plant lover, cookie monster, shoe fiend
19864 stories
·
21 followers

Nanaimo cyclist from viral video says he was pushed - YouTube

1 Share
Read the whole story
sarcozona
5 hours ago
reply
Epiphyte City
Share this story
Delete

"Divine Feminine" Advice on TikTok Is Just Part of the Alt-Right Pipeline | Teen Vogue

1 Share

Of course, the portrayal of this idea on social media isn’t the full scope — some ideas reflected in divine femininity have been around for a long time, and it’s one that some find deep independence and empowerment through. Online, divine femininity borrows heavily from ancient spiritual traditions, though not always responsibly, according to Neha Chandrachud, a writer and cultural critic who often discusses religious and conservative movements.

“Divine femininity is really a misinterpretation of a lot of … Eastern philosophical principles about embodying the masculine and the feminine within,” Chandrachud says. “When you remove these ideas of Eastern spirituality from their original containers and you commodify them under this Western principle, you end up with a very bastardized idea of what masculinity and femininity are supposed to be.”

As the conversation has migrated to social media, many of the posts encouraging this idea are little more than repackaging rigid gender roles as spiritual self-help. Content creator Jess Britvich explores common entry-points to far-right ideology. She defines divine femininity as “the belief that men and women are biologically destined for certain character traits and that by embracing these traits, individuals will find happiness, fulfillment in relationships, and ultimately, purpose in life.”

Britvich says that this content "plays a huge role" in the alt-right pipeline for women. Although engaging with this content isn’t inherently dangerous for everyone, it can lead you down a slippery slope, Britvich says. “It’s gender essentialism, plain and simple, and gender essentialism is central to authoritarian ideologies like fascism and Christian nationalism. It tells people you are either a man or a woman, and your role is fixed.”

Many Divine Femininity influencers draw on prehistory to justify gender roles, using the idea that “men were hunters.” They advocate a return to our “ancestral roles” in which men were “providers.” However, it seems history wasn’t that simple. Cara Ocobock, PhD, and Sarah Lacy, PhD, co-authored two studies showing that prehistoric women commonly hunted, and that our ancestors’ roles weren’t so rigid.

“There's no one universal way to be human,” says Ocobock. “There is no one universal pattern of femininity or masculinity, or typical gender roles.” When asked why she thought Divine Femininity creators invoke prehistory or biology, she said, “People are picking and choosing various versions of our evolutionary past in order to justify modern day behavior.”

But this rigid categorization might be part of Divine Femininity’s appeal. Britvich suggests that it plays on our love for self-categorization, appealing to millennials who grew up on BuzzFeed quizzes and Gen Zers who subscribe to certain aesthetic identities. As Ocobock puts it, “Humans like to organize things by categories and then, of course, apply a hierarchy to them.”

It seems Divine Femininity also taps into a deeper desire. Many young people are losing interest in the life path set out by previous generations, feeling burnt out by the rise of hustle culture and disillusioned with the promises it makes. For women, this can feel particularly frustrating. A large part of a generation of daughters watched their mothers work doubles — career and home — while their fathers clocked off at 5 p.m. Although pop feminism told women we could do anything, our childhoods suggested we’d have to do everything. For women of color, the message cuts deeper. Many women of color feel overworked, unprotected, and robbed of the ability to be soft.

Read the whole story
sarcozona
5 hours ago
reply
Epiphyte City
Share this story
Delete

The bitter truth is that cheaper housing means a retirement crisis for homeowners - The Globe and Mail

1 Share
Read the whole story
sarcozona
15 hours ago
reply
Epiphyte City
Share this story
Delete

Fifty years of monoclonals: the past, present and future of antibody therapeutics | Nature Reviews Immunology

1 Comment
  1. Köhler, G. & Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495–497 (1975). Ground-breaking invention of hybridoma technology that was a key step towards this modern era of antibody-based therapeutics.

    PubMed  Google Scholar 

  2. Bradbury, A. & Plückthun, A. Reproducibility: standardize antibodies used in research. Nature 518, 27–29 (2015).

    CAS  PubMed  Google Scholar 

  3. Uhr, J. W. The 1984 Nobel Prize in Medicine. Science 226, 1025–1028 (1984).

    CAS  PubMed  Google Scholar 

  4. Boulianne, G. L., Hozumi, N. & Shulman, M. J. Production of functional chimaeric mouse/human antibody. Nature 312, 643–646 (1984). Together with ref. 5 is the first demonstration of chimerization of a murine monoclonal antibody.

    CAS  PubMed  Google Scholar 

  5. Morrison, S. L., Johnson, M. J., Herzenberg, L. A. & Oi, V. T. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc. Natl Acad. Sci. USA 81, 6851–6855 (1984). Together with ref. 4 is the first demonstration of chimerization of a murine monoclonal antibody.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Jones, P. T., Dear, P. H., Foote, J., Neuberger, M. S. & Winter, G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 321, 522–525 (1986). First demonstration of humanization of a murine antibody that, together with refs. 7 and 8, eventually led to at least 105 approved humanized antibody therapeutics.

    CAS  PubMed  Google Scholar 

  7. Riechmann, L., Clark, M., Waldmann, H. & Winter, G. Reshaping human antibodies for therapy. Nature 332, 323–327 (1988).

    CAS  PubMed  Google Scholar 

  8. Verhoeyen, M., Milstein, C. & Winter, G. Reshaping human antibodies: grafting an antilysozyme activity. Science 239, 1534–1536 (1988).

    CAS  PubMed  Google Scholar 

  9. Wilkinson, I. & Hale, G. Systematic analysis of the varied designs of 819 therapeutic antibodies and Fc fusion proteins assigned international nonproprietary names. MAbs 14, 2123299 (2022).

    PubMed  PubMed Central  Google Scholar 

  10. Carter, P. J. & Rajpal, A. Designing antibodies as therapeutics. Cell 185, 2789–2805 (2022).

    CAS  PubMed  Google Scholar 

  11. Paul, S. et al. Cancer therapy with antibodies. Nat. Rev. Cancer 24, 399–426 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Carter, P. J. & Quarmby, V. Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics. Nat. Rev. Drug Discov. 23, 898–913 (2024).

    CAS  PubMed  Google Scholar 

  13. Qian, L. et al. The dawn of a new era: targeting the “undruggables” with antibody-based therapeutics. Chem. Rev. 123, 7782–7853 (2023).

    CAS  PubMed  Google Scholar 

  14. Brown, D. G., Wobst, H. J., Kapoor, A., Kenna, L. A. & Southall, N. Clinical development times for innovative drugs. Nat. Rev. Drug Discov. 21, 793–794 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Genetta, T. B. & Mauro, V. F. ABCIXIMAB: a new antiaggregant used in angioplasty. Ann. Pharmacother. 30, 251–257 (1996).

    CAS  PubMed  Google Scholar 

  16. Vincenti, F. Daclizumab: novel biologic immunoprophylaxis for prevention of acute rejection in renal transplantation. Transplant. Proc. 31, 2206–2207 (1999).

    CAS  PubMed  Google Scholar 

  17. Bain, B. & Brazil, M. Adalimumab. Nat. Rev. Drug Discov. 2, 693–694 (2003).

    CAS  PubMed  Google Scholar 

  18. US Food and Drug Administration. Prescribing information, HUMIRA® (adalimumab) injection, for subcutaneous use. fda.gov https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125057s423lbl.pdf (2023).

  19. Gibbons, J. B., Laber, M. & Bennett, C. L. Humira: the first $20 billion drug. Am. J. Manag. Care 29, 78–80 (2023).

    PubMed  Google Scholar 

  20. Crescioli, S. et al. Antibodies to watch in 2025. MAbs 17, 2443538 (2025). Most recent of a regular series of articles reviewing recently approved and registrational stage antibody therapeutics.

    PubMed  Google Scholar 

  21. Dumontet, C., Reichert, J. M., Senter, P. D., Lambert, J. M. & Beck, A. Antibody–drug conjugates come of age in oncology. Nat. Rev. Drug Discov. 22, 641–661 (2023).

    CAS  PubMed  Google Scholar 

  22. Goebeler, M. E., Stuhler, G. & Bargou, R. Bispecific and multispecific antibodies in oncology: opportunities and challenges. Nat. Rev. Clin. Oncol. 21, 539–560 (2024).

    PubMed  Google Scholar 

  23. Klein, C., Brinkmann, U., Reichert, J. M. & Kontermann, R. E. The present and future of bispecific antibodies for cancer therapy. Nat. Rev. Drug Discov. 23, 301–319 (2024).

    CAS  PubMed  Google Scholar 

  24. Pirkalkhoran, S. et al. Bioengineering of antibody fragments: challenges and opportunities. Bioengineering 10, 122 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Silver, A. B., Leonard, E. K., Gould, J. R. & Spangler, J. B. Engineered antibody fusion proteins for targeted disease therapy. Trends Pharmacol. Sci. 42, 1064–1081 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Larbouret, C., Gros, L., Pèlegrin, A. & Chardès, T. Improving biologics’ effectiveness in clinical oncology: from the combination of two monoclonal antibodies to oligoclonal antibody mixtures. Cancers 13, 4620 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Cappell, K. M. & Kochenderfer, J. N. Long-term outcomes following CAR T cell therapy: what we know so far. Nat. Rev. Clin. Oncol. 20, 359–371 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Moolten, F. L. & Cooperband, S. R. Selective destruction of target cells by diphtheria toxin conjugated to antibody directed against antigens on the cells. Science 169, 68–70 (1970). First demonstration of an immunotoxin for directed killing of target cells.

    CAS  PubMed  Google Scholar 

  29. Casi, G. & Neri, D. Antibody-drug conjugates and small molecule-drug conjugates: opportunities and challenges for the development of selective anticancer cytotoxic agents. J. Med. Chem. 58, 8751–8761 (2015).

    CAS  PubMed  Google Scholar 

  30. Sedalacek, H.-H. et al. (eds) Antibodies as Carriers of Cytotoxicity. Contributions to Oncology Vol. 43 (eds Huber, P & Queisser, W.) (Karger, 1992).

  31. Mahalingaiah, P. K. et al. Potential mechanisms of target-independent uptake and toxicity of antibody-drug conjugates. Pharmacol. Ther. 200, 110–125 (2019).

    CAS  PubMed  Google Scholar 

  32. Doronina, S. O. et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug. Chem. 17, 114–124 (2006).

    CAS  PubMed  Google Scholar 

  33. Doronina, S. O. et al. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat. Biotechnol. 21, 778–784 (2003). First publication of ADCs with auristatin payloads, which has led to the approval of at least nine such ADCs.

    CAS  PubMed  Google Scholar 

  34. Bross, P. F. et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin. Cancer Res. 7, 1490–1496 (2001).

    CAS  PubMed  Google Scholar 

  35. Norsworthy, K. J. et al. FDA approval summary: mylotarg for treatment of patients with relapsed or refractory CD33-positive acute myeloid leukemia. Oncologist 23, 1103–1108 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Junutula, J. R. et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat. Biotechnol. 26, 925–932 (2008).

    CAS  PubMed  Google Scholar 

  37. Lehar, S. M. et al. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature 527, 323–328 (2015).

    CAS  PubMed  Google Scholar 

  38. Dragovich, P. S. Degrader-antibody conjugates. Chem. Soc. Rev. 51, 3886–3897 (2022).

    CAS  PubMed  Google Scholar 

  39. Poudel, Y. B., Thakore, R. R. & Chekler, E. P. The new frontier: merging molecular glue degrader and antibody-drug conjugate modalities to overcome strategic challenges. J. Med. Chem. 67, 15996–16001 (2024).

    CAS  PubMed  Google Scholar 

  40. Nisonoff, A., Wissler, F. C. & Lipman, L. N. Properties of the major component of a peptic digest of rabbit antibody. Science 132, 1770–1771 (1960). First demonstration of the concept of bispecific antibodies.

    CAS  PubMed  Google Scholar 

  41. Seimetz, D., Lindhofer, H. & Bokemeyer, C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat. Rev. 36, 458–467 (2010). First approved bispecific: catumaxomab (targeting EpCAM and CD3; TCE).

    CAS  PubMed  Google Scholar 

  42. Milstein, C. & Cuello, A. C. Hybrid hybridomas and their use in immunohistochemistry. Nature 305, 537–540 (1983).

    CAS  PubMed  Google Scholar 

  43. Staerz, U. D., Kanagawa, O. & Bevan, M. J. Hybrid antibodies can target sites for attack by T cells. Nature 314, 628–631 (1985). First demonstration of the concept of using bispecific antibodies to direct the killing of tumour cells by T cells, leading to at least nine such approved TCEs.

    CAS  PubMed  Google Scholar 

  44. Underwood, D. J., Bettencourt, J. & Jawad, Z. The manufacturing considerations of bispecific antibodies. Expert Opin. Biol. Ther. 22, 1043–1065 (2022).

    CAS  PubMed  Google Scholar 

  45. Brinkmann, U. & Kontermann, R. E. The making of bispecific antibodies. MAbs 9, 182–212 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Spiess, C., Zhai, Q. & Carter, P. J. Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol. Immunol. 67, 95–106 (2015).

    CAS  PubMed  Google Scholar 

  47. Mack, M., Riethmüller, G. & Kufer, P. A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity. Proc. Natl Acad. Sci. USA 92, 7021–7025 (1995). First demonstration of a TCE bispecific antibody (CD19 and CD3) in tandem scFv (BiTE) format that eventually led to blinatumomab.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Ridgway, J. B., Presta, L. G. & Carter, P. ‘Knobs-into-holes’ engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng. 9, 617–621 (1996). First demonstration of ‘knobs-into-holes’ technology that after refinement (ref. 49 and ref. 52), has been widely used for Fc heterodimerization, including for at least three approved bispecific antibodies: mosunetuzumab, glofitamab-gxbm and faricimab-svoa.

    CAS  PubMed  Google Scholar 

  49. Atwell, S., Ridgway, J. B., Wells, J. A. & Carter, P. Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library. J. Mol. Biol. 270, 26–35 (1997).

    CAS  PubMed  Google Scholar 

  50. Schaefer, W. et al. Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies. Proc. Natl Acad. Sci. USA 108, 11187–11192 (2011). First demonstration of CrossMab technology that has been used to generate at least two approved bispecific antibodies: glofitamab-gxbm and faricimab-svoa.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Surowka, M., Schaefer, W. & Klein, C. Ten years in the making: application of CrossMab technology for the development of therapeutic bispecific antibodies and antibody fusion proteins. MAbs 13, 1967714 (2021).

    PubMed  PubMed Central  Google Scholar 

  52. Merchant, A. M. et al. An efficient route to human bispecific IgG. Nat. Biotechnol. 16, 677–681 (1998). First use of common light chains, a technology subsequently used for at least four approved bispecific antibodies: emicizumab, odronextamab, zenocutuzumab-zbco and linvoseltamab.

    CAS  PubMed  Google Scholar 

  53. Labrijn, A. F. et al. Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange. Proc. Natl Acad. Sci. USA 110, 5145–5150 (2013). First demonstration of DuoBody technology that has been used for at least four approved bispecific antibodies: amivantamab-vmjw, epcoritamab-bysp, talquetamab-tgvs and teclistamab-cqyv.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Von Kreudenstein, T. S. et al. Improving biophysical properties of a bispecific antibody scaffold to aid developability: quality by molecular design. MAbs 5, 646–654 (2013).

    Google Scholar 

  55. Yao, Y., Hu, Y. & Wang, F. Trispecific antibodies for cancer immunotherapy. Immunol. Rev. 169, 389–399 (2023).

    CAS  Google Scholar 

  56. Cheson, B. D. & Leonard, J. P. Monoclonal antibody therapy for B-cell non-Hodgkin’s lymphoma. N. Engl. J. Med. 359, 613–626 (2008).

    CAS  PubMed  Google Scholar 

  57. Reff, M. E. et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83, 435–445 (1994).

    CAS  PubMed  Google Scholar 

  58. Alduaij, W. et al. Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies. Blood 117, 4519–4529 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Ghosh, A. et al. Decoding the molecular interplay of CD20 and therapeutic antibodies with fast volumetric nanoscopy. Science 387, eadq4510 (2025).

    CAS  PubMed  Google Scholar 

  60. Weng, W. K. & Levy, R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J. Clin. Oncol. 21, 3940–3947 (2003).

    CAS  PubMed  Google Scholar 

  61. Cartron, G. et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 99, 754–758 (2002). First demonstration of the clinical activity of an antibody (rituximab) correlating with polymorphisms in an Fcγ receptor (FcγRIIIA).

    CAS  PubMed  Google Scholar 

  62. Mossner, E. et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 115, 4393–4402 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Cheson, B. D. et al. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J. Clin. Oncol. 36, 2259–2266 (2018).

    CAS  PubMed  Google Scholar 

  64. Goede, V. et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N. Engl. J. Med. 370, 1101–1110 (2014).

    CAS  PubMed  Google Scholar 

  65. Townsend, W. et al. Obinutuzumab versus rituximab immunochemotherapy in previously untreated iNHL: final results from the GALLIUM study. Hemasphere 7, e919 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Vitolo, U. et al. Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma. J. Clin. Oncol. 35, 3529–3537 (2017).

    CAS  PubMed  Google Scholar 

  67. Davies, A. et al. Obinutuzumab in the treatment of B-cell malignancies: a comprehensive review. Future Oncol. 18, 2943–2966 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Marcus, R. et al. Obinutuzumab for the first-line treatment of follicular lymphoma. N. Engl. J. Med. 377, 1331–1344 (2017).

    CAS  PubMed  Google Scholar 

  69. Lazar, G. A. et al. Engineered antibody Fc variants with enhanced effector function. Proc. Natl Acad. Sci. USA 103, 4005–4010 (2006). Extensive mutational analysis of IgG1 Fc to tailor effector functions.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Salles, G. et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 21, 978–988 (2020).

    CAS  PubMed  Google Scholar 

  71. Duell, J. et al. Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety findings in the phase II L-MIND study. Haematologica 109, 553–566 (2024).

    CAS  PubMed  Google Scholar 

  72. Hiraga, J. et al. Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance. Blood 113, 4885–4893 (2009).

    CAS  PubMed  Google Scholar 

  73. Rehman, R. U., Anjum, A. F. & Fatima, R. Tarlatamab and the future of immunotherapy: a new approach to small cell lung cancer. Curr. Ther. Res. Clin. Exp. 102, 100773 (2025).

    PubMed  Google Scholar 

  74. Kantarjian, H. et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N. Engl. J. Med. 376, 836–847 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Löffler, A. et al. A recombinant bispecific single-chain antibody, CD19 × CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood 95, 2098–2103 (2000).

    PubMed  Google Scholar 

  76. Mocquot, P., Mossazadeh, Y., Lapierre, L., Pineau, F. & Despas, F. The pharmacology of blinatumomab: state of the art on pharmacodynamics, pharmacokinetics, adverse drug reactions and evaluation in clinical trials. J. Clin. Pharm. Ther. 47, 1337–1351 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Elmeliegy, M. et al. Dosing strategies and quantitative clinical pharmacology for bispecific T-cell engagers development in oncology. Clin. Pharmacol. Ther. 116, 637–646 (2024).

    CAS  PubMed  Google Scholar 

  78. Budde, L. E. et al. Durable responses with mosunetuzumab in relapsed/refractory indolent and aggressive B-cell non-Hodgkin lymphomas: extended follow-up of a phase I/II study. J. Clin. Oncol. 42, 2250–2256 (2024).

    CAS  PubMed  Google Scholar 

  79. Dickinson, M. J. et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N. Engl. J. Med. 387, 2220–2231 (2022).

    CAS  PubMed  Google Scholar 

  80. Thieblemont, C. et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial. J. Clin. Oncol. 41, 2238–2247 (2023).

    CAS  PubMed  Google Scholar 

  81. Kim, T. M. et al. Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma. Ann. Oncol. 35, 1039–1047 (2024).

    CAS  PubMed  Google Scholar 

  82. Moreau, P. et al. Teclistamab in relapsed or refractory multiple myeloma. N. Engl. J. Med. 387, 495–505 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Lesokhin, A. M. et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat. Med. 29, 2259–2267 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Avigan, Z. M., Rattu, M. A. & Richter, J. An evaluation of linvoseltamab for treatment of relapsed/refractory multiple myeloma. Expert Opin. Biol. Ther. 25, 221–228 (2025).

    CAS  PubMed  Google Scholar 

  85. Chari, A. et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N. Engl. J. Med. 387, 2232–2244 (2022).

    CAS  PubMed  Google Scholar 

  86. Bacac, M. et al. CD20-TCB with obinutuzumab pretreatment as next-generation treatment of hematologic malignancies. Clin. Cancer Res. 24, 4785–4797 (2018).

    CAS  PubMed  Google Scholar 

  87. Guedan, S., Ruella, M. & June, C. H. Emerging cellular therapies for cancer. Annu. Rev. Immunol. 37, 145–171 (2019).

    CAS  PubMed  Google Scholar 

  88. Haydu, J. E. & Abramson, J. S. The rules of T-cell engagement: current state of CAR T cells and bispecific antibodies in B-cell lymphomas. Blood Adv. 8, 4700–4710 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Swan, D., Madduri, D. & Hocking, J. CAR-T cell therapy in multiple myeloma: current status and future challenges. Blood Cancer J. 14, 206 (2024).

    PubMed  PubMed Central  Google Scholar 

  90. Anderson, N. D. et al. Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia. Nat. Med. 29, 1700–1709 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Witzig, T. E. et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J. Clin. Oncol. 20, 2453–2463 (2002).

    CAS  PubMed  Google Scholar 

  92. Horning, S. J. et al. Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J. Clin. Oncol. 23, 712–719 (2005).

    CAS  PubMed  Google Scholar 

  93. Kantarjian, H. M. et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N. Engl. J. Med. 375, 740–753 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Tilly, H. et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N. Engl. J. Med. 386, 351–363 (2022).

    CAS  PubMed  Google Scholar 

  95. Caimi, P. F. et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 22, 790–800 (2021).

    CAS  PubMed  Google Scholar 

  96. Tai, Y. T. et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood 123, 3128–3138 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Dimopoulos, M. A. et al. Efficacy and safety of single-agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-3): a phase 3, open-label, randomised study. Lancet Haematol. 10, e801–e812 (2023).

    CAS  PubMed  Google Scholar 

  98. Kreitman, R. J. et al. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia 32, 1768–1777 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Khoury, R. et al. Mechanisms of resistance to antibody-drug conjugates. Int. J. Mol. Sci. 24, 9674 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Edwards, J. C. et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350, 2572–2581 (2004). First demonstration of efficacy of rituximab, a chimeric anti-CD20 antibody, in a randomized double-blind placebo-controlled trial of patients with rheumatoid arthritis.

    CAS  PubMed  Google Scholar 

  101. Cohen, S. B. et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 54, 2793–2806 (2006).

    CAS  PubMed  Google Scholar 

  102. Joly, P. et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet 389, 2031–2040 (2017).

    CAS  PubMed  Google Scholar 

  103. Jones, R. B. et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N. Engl. J. Med. 363, 211–220 (2010).

    CAS  PubMed  Google Scholar 

  104. Martin, F. & Chan, A. C. B cell immunobiology in disease: evolving concepts from the clinic. Annu. Rev. Immunol. 24, 467–496 (2006).

    CAS  PubMed  Google Scholar 

  105. Merrill, J. T. et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 62, 222–233 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Rovin, B. H. et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the lupus nephritis assessment with rituximab study. Arthritis Rheum. 64, 1215–1226 (2012).

    CAS  PubMed  Google Scholar 

  107. Gomez Mendez, L. M. et al. Peripheral blood B cell depletion after rituximab and complete response in lupus nephritis. Clin. J. Am. Soc. Nephrol. 13, 1502–1509 (2018).

    PubMed  PubMed Central  Google Scholar 

  108. Gong, Q. et al. Importance of cellular microenvironment and circulatory dynamics in B cell immunotherapy. J. Immunol. 174, 817–826 (2005).

    CAS  PubMed  Google Scholar 

  109. Ahuja, A. et al. Depletion of B cells in murine lupus: efficacy and resistance. J. Immunol. 179, 3351–3361 (2007).

    CAS  PubMed  Google Scholar 

  110. Marinov, A. D. et al. The type II anti-CD20 antibody obinutuzumab (GA101) is more effective than rituximab at depleting B cells and treating disease in a murine lupus model. Arthritis Rheumatol. 73, 826–836 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Furie, R. A. et al. Efficacy and safety of obinutuzumab in active lupus nephritis. N. Engl. J. Med. 392, 1471–1483 (2025).

    CAS  PubMed  Google Scholar 

  112. Hauser, S. L. et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N. Engl. J. Med. 358, 676–688 (2008).

    CAS  PubMed  Google Scholar 

  113. Hawker, K. et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann. Neurol. 66, 460–471 (2009).

    CAS  PubMed  Google Scholar 

  114. Dunn, N. et al. Rituximab in multiple sclerosis: frequency and clinical relevance of anti-drug antibodies. Mult. Scler. 24, 1224–1233 (2018).

    CAS  PubMed  Google Scholar 

  115. Wolf, A. B. et al. Rituximab-induced serum sickness in multiple sclerosis patients. Mult. Scler. Relat. Disord. 36, 101402 (2019).

    PubMed  Google Scholar 

  116. Wincup, C. et al. Anti-rituximab antibodies demonstrate neutralizing capacity, associate with lower circulating drug levels and earlier relapse in lupus. Rheumatology 62, 2601–2610 (2023).

    CAS  PubMed  Google Scholar 

  117. Hauser, S. L. et al. Ofatumumab versus teriflunomide in multiple sclerosis. N. Engl. J. Med. 383, 546–557 (2020).

    CAS  PubMed  Google Scholar 

  118. Hauser, S. L. et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N. Engl. J. Med. 376, 221–234 (2017). First phase III demonstration of efficacy of ocrelizumab, a humanized anti-CD20 antibody, compared with interferon β1a standard of care in relapsing multiple sclerosis.

    CAS  PubMed  Google Scholar 

  119. Montalban, X. et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N. Engl. J. Med. 376, 209–220 (2017). First phase III demonstration of efficacy of ocrelizumab, a humanized anti-CD20 antibody, in PPMS.

    CAS  PubMed  Google Scholar 

  120. Fischbach, F. et al. CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis. Med 5, 550–558 e552 (2024).

    CAS  PubMed  Google Scholar 

  121. Müller, F. et al. CD19 CAR T-cell therapy in autoimmune disease – a case series with follow-up. N. Engl. J. Med. 390, 687–700 (2024).

    PubMed  Google Scholar 

  122. Swain, S. M., Shastry, M. & Hamilton, E. Targeting HER2-positive breast cancer: advances and future directions. Nat. Rev. Drug Discov. 22, 101–126 (2023).

    CAS  PubMed  Google Scholar 

  123. Carter, P. et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc. Natl Acad. Sci. USA 89, 4285–4289 (1992). Humanization of a murine anti-HER2 antibody, 4D5, that led to trastuzumab, the first antibody to be approved for breast cancer.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Hudziak, R. M. et al. p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol. Cell. Biol. 9, 1165–1172 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783–792 (2001). Demonstration that the humanized anti-HER2 antibody trastuzumab increases the clinical benefit of chemotherapy in metastatic breast cancer that overexpresses HER2.

    CAS  PubMed  Google Scholar 

  126. Jorgensen, J. T. et al. A companion diagnostic with significant clinical impact in treatment of breast and gastric cancer. Front. Oncol. 11, 676939 (2021).

    PubMed  PubMed Central  Google Scholar 

  127. Slamon, D. et al. Adjuvant trastuzumab in HER2-positive breast cancer. N. Engl. J. Med. 365, 1273–1283 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Agus, D. B. et al. Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell 2, 127–137 (2002).

    CAS  PubMed  Google Scholar 

  129. Shao, Z. et al. Efficacy, safety, and tolerability of pertuzumab, trastuzumab, and docetaxel for patients with early or locally advanced ERBB2-positive breast cancer in Asia: the PEONY phase 3 randomized clinical trial. JAMA Oncol. 6, e193692 (2020).

    PubMed  Google Scholar 

  130. von Minckwitz, G. et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N. Engl. J. Med. 377, 122–131 (2017).

    Google Scholar 

  131. Swain, S. M. et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N. Engl. J. Med. 372, 724–734 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Gao, J. J. et al. FDA approval summary: pertuzumab, trastuzumab, and hyaluronidase-zzxf injection for subcutaneous use in patients with HER2-positive breast cancer. Clin. Cancer Res. 27, 2126–2129 (2021).

    CAS  PubMed  Google Scholar 

  133. Hurvitz, S. A. et al. Analysis of Fcγ receptor IIIa and IIa polymorphisms: lack of correlation with outcome in trastuzumab-treated breast cancer patients. Clin. Cancer Res. 18, 3478–3486 (2012).

    CAS  PubMed  Google Scholar 

  134. Tamura, K. et al. FcγR2A and 3A polymorphisms predict clinical outcome of trastuzumab in both neoadjuvant and metastatic settings in patients with HER2-positive breast cancer. Ann. Oncol. 22, 1302–1307 (2011).

    CAS  PubMed  Google Scholar 

  135. Wang, D. S. et al. FcγRIIA and IIIA polymorphisms predict clinical outcome of trastuzumab-treated metastatic gastric cancer. OncoTargets Ther. 10, 5065–5076 (2017).

    Google Scholar 

  136. Nordstrom, J. L. et al. Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcγ receptor binding properties. Breast Cancer Res. 13, R123 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Fendly, B. M. et al. Characterization of murine monoclonal antibodies reactive to either the human epidermal growth factor receptor or HER2/neu gene product. Cancer Res. 50, 1550–1558 (1990).

    CAS  PubMed  Google Scholar 

  138. Rugo, H. S. et al. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer: a phase 3 randomized clinical trial. JAMA Oncol. 7, 573–584 (2021).

    PubMed  Google Scholar 

  139. Lewis Phillips, G. D. et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 68, 9280–9290 (2008).

    CAS  PubMed  Google Scholar 

  140. Verma, S. et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 367, 1783–1791 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. von Minckwitz, G. et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N. Engl. J. Med. 380, 617–628 (2019).

    Google Scholar 

  142. Ogitani, Y. et al. DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin. Cancer Res. 22, 5097–5108 (2016).

    CAS  PubMed  Google Scholar 

  143. Ogitani, Y., Hagihara, K., Oitate, M., Naito, H. & Agatsuma, T. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci. 107, 1039–1046 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Narayan, P. et al. FDA approval summary: fam-trastuzumab deruxtecan-nxki for the treatment of unresectable or metastatic HER2-positive breast cancer. Clin. Cancer Res. 27, 4478–4485 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Modi, S. et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N. Engl. J. Med. 382, 610–621 (2020).

    CAS  PubMed  Google Scholar 

  146. Modi, S. et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N. Engl. J. Med. 387, 9–20 (2022). Landmark clinical study demonstrating the efficacy of the ADC, trastuzumab deruxtecan, in previously treated HER2-low breast cancer.

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Prescribing information, ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use. fda.gov https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761139s032s035lbl.pdf (2025).

  148. Weisser, N. E. et al. An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity. Nat. Commun. 14, 1394 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Harding, J. J. et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncol. 24, 772–782 (2023).

    CAS  PubMed  Google Scholar 

  150. Keam, S. J. Zanidatamab: first approval. Drugs 85, 707–714 (2025).

    CAS  PubMed  Google Scholar 

  151. Jonna, S. et al. Detection of NRG1 gene fusions in solid tumors. Clin. Cancer Res. 25, 4966–4972 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Werr, L. et al. CD74-NRG1 fusions are oncogenic in vivo and induce therapeutically tractable ERBB2:ERBB3 heterodimerization. Mol. Cancer Ther. 21, 821–830 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Schram, A. M. et al. Efficacy of zenocutuzumab in NRG1 fusion-positive cancer. N. Engl. J. Med. 392, 566–576 (2025).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Press, M. F., Cordon-Cardo, C. & Slamon, D. J. Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene 5, 953–962 (1990).

    CAS  PubMed  Google Scholar 

  155. Gordon, L. I. et al. Blockade of the erbB2 receptor induces cardiomyocyte death through mitochondrial and reactive oxygen species-dependent pathways. J. Biol. Chem. 284, 2080–2087 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Seidman, A. et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J. Clin. Oncol. 20, 1215–1221 (2002).

    CAS  PubMed  Google Scholar 

  157. Morgan, R. A. et al. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol. Ther. 18, 843–851 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Slaga, D. et al. Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3. Sci. Transl. Med. 10, eaat5775 (2018). Avidity engineering of a TCE bispecific antibody (HER2 and CD3) to enhance the selectivity of cytotoxicity towards tumour cells overexpressing HER2.

    PubMed  Google Scholar 

  159. Oostindie, S. C. et al. Logic-gated antibody pairs that selectively act on cells co-expressing two antigens. Nat. Biotechnol. 40, 1509–1519 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Davis, J. D. et al. Subcutaneous administration of monoclonal antibodies: pharmacology, delivery, immunogenicity, and learnings from applications to clinical development. Clin. Pharmacol. Ther. 115, 422–439 (2024).

    CAS  PubMed  Google Scholar 

  161. Lang, J. J. et al. Patient-reported disruptions to cancer care during the COVID-19 pandemic: a national cross-sectional study. Cancer Med. 12, 4773–4785 (2023).

    PubMed  Google Scholar 

  162. Lambert, M. A. & Finlay, W. J. J. in Orphan Drugs and Rare Disease. Drug Discovery Series 38 (eds D. C. Pryde & M. J. Palmer) Ch. 14, 401–418 (Royal Society of Chemistry, 2014).

  163. Prescribing information, Soliris (eculizumab) for intravenous infusion. fda.gov https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125166s448,761108s038lbl.pdf (2025).

  164. Sheridan, D. et al. Design and preclinical characterization of ALXN1210: a novel anti-C5 antibody with extended duration of action. PLoS ONE 13, e0195909 (2018).

    PubMed  PubMed Central  Google Scholar 

  165. Zalevsky, J. et al. Enhanced antibody half-life improves in vivo activity. Nat. Biotechnol. 28, 157–159 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Prescribing information, Ultomiris (ravulizumab-cwvz) injection, for intravenous use. fda.gov https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761108s037lbl.pdf (2024).

  167. Viola, M. et al. Subcutaneous delivery of monoclonal antibodies: how do we get there? J. Control. Release 286, 301–314 (2018).

    CAS  PubMed  Google Scholar 

  168. Strickley, R. G. & Lambert, W. J. A review of formulations of commercially available antibodies. J. Pharm. Sci. 110, 2590–2608 e2556 (2021).

    CAS  PubMed  Google Scholar 

  169. Zarzar, J. et al. High concentration formulation developability approaches and considerations. MAbs 15, 2211185 (2023).

    PubMed  PubMed Central  Google Scholar 

  170. Sánchez-Félix, M., Burke, M., Chen, H. H., Patterson, C. & Mittal, S. Predicting bioavailability of monoclonal antibodies after subcutaneous administration: open innovation challenge. Adv. Drug Deliv. Rev. 167, 66–77 (2020).

    PubMed  Google Scholar 

  171. Sauna, Z. E., Jawa, V., Balu-Iyer, S. & Chirmule, N. Understanding preclinical and clinical immunogenicity risks in novel biotherapeutics development. Front. Immunol. 14, 1151888 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Swanson, S. J. What are clinically significant anti-drug antibodies and why is it important to identify them. Front. Immunol. 15, 1401178 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Homšek, A. et al. Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology. J. Oncol. Pharm. Pract. 29, 431–440 (2022).

    PubMed  Google Scholar 

  174. Dai, J. et al. Variable domain mutational analysis to probe the molecular mechanisms of high viscosity of an IgG1 antibody. MAbs 16, 2304282 (2024).

    PubMed  PubMed Central  Google Scholar 

  175. Nichols, P. et al. Rational design of viscosity reducing mutants of a monoclonal antibody: hydrophobic versus electrostatic inter-molecular interactions. MAbs 7, 212–230 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Yadav, S. et al. Establishing a link between amino acid sequences and self-associating and viscoelastic behavior of two closely related monoclonal antibodies. Pharm. Res. 28, 1750–1764 (2011).

    CAS  PubMed  Google Scholar 

  177. Heisler, J., Kovner, D., Izadi, S., Zarzar, J. & Carter, P. J. Modulation of the high concentration viscosity of IgG1 antibodies using clinically validated Fc mutations. MAbs 16, 2379560 (2024).

    PubMed  PubMed Central  Google Scholar 

  178. Igawa, T., Haraya, K. & Hattori, K. Sweeping antibody as a novel therapeutic antibody modality capable of eliminating soluble antigens from circulation. Immunol. Rev. 270, 132–151 (2016).

    CAS  PubMed  Google Scholar 

  179. Igawa, T. et al. Engineered monoclonal antibody with novel antigen-sweeping activity in vivo. PLoS ONE 8, e63236 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Igawa, T. et al. Antibody recycling by engineered pH-dependent antigen binding improves the duration of antigen neutralization. Nat. Biotechnol. 28, 1203–1207 (2010). First demonstration that engineering an antibody for pH-dependent antigen binding could extend its plasma life and duration of antigen neutralization in vivo.

    CAS  PubMed  Google Scholar 

  181. Sampei, Z. et al. Antibody engineering to generate SKY59, a long-acting anti-C5 recycling antibody. PLoS ONE 13, e0209509 (2018).

    PubMed  PubMed Central  Google Scholar 

  182. Fukuzawa, T. et al. Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases. Sci. Rep. 7, 1080 (2017).

    PubMed  PubMed Central  Google Scholar 

  183. Callaway, E. Chemistry Nobel goes to developers of AlphaFold AI that predicts protein structures. Nature 634, 525–526 (2024).

    CAS  PubMed  Google Scholar 

  184. Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021). First release of AlphaFold, an artificial intelligence tool that predicts protein structures from amino acid sequences with previously unprecedented speed and accuracy, with great potential to accelerate basic research and drug discovery.

    CAS  PubMed  PubMed Central  Google Scholar 

  185. Vazquez Torres, S. et al. De novo design of high-affinity binders of bioactive helical peptides. Nature 626, 435–442 (2024).

    CAS  PubMed  Google Scholar 

  186. Ichikawa, D. M. et al. A universal deep-learning model for zinc finger design enables transcription factor reprogramming. Nat. Biotechnol. 41, 1117–1129 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Hie, B. L. et al. Efficient evolution of human antibodies from general protein language models. Nat. Biotechnol. 42, 275–283 (2024).

    CAS  PubMed  Google Scholar 

  188. Frey, N. C. et al. Lab-in-the-loop therapeutic antibody design with deep learning. Preprint at bioRxiv https://doi.org/10.1101/2025.02.19.639050 (2025).

  189. Li, L. et al. Machine learning optimization of candidate antibody yields highly diverse sub-nanomolar affinity antibody libraries. Nat. Commun. 14, 3454 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  190. Harvey, E. P. et al. An in silico method to assess antibody fragment polyreactivity. Nat. Commun. 13, 7554 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  191. Sweet-Jones, J. & Martin, A. C. R. An antibody developability triaging pipeline exploiting protein language models. MAbs 17, 2472009 (2025).

    PubMed  PubMed Central  Google Scholar 

  192. Kalejaye, L. A. et al. Accelerating high-concentration monoclonal antibody development with large-scale viscosity data and ensemble deep learning. MAbs 17, 2483944 (2025).

    PubMed  PubMed Central  Google Scholar 

  193. Liang, W. C. et al. Structure- and machine learning-guided engineering demonstrate that a non-canonical disulfide in an anti-PD-1 rabbit antibody does not impede antibody developability. MAbs 16, 2309685 (2024).

    PubMed  PubMed Central  Google Scholar 

  194. Wang, H., Hao, X., He, Y. & Fan, L. AbImmPred: an immunogenicity prediction method for therapeutic antibodies using AntiBERTy-based sequence features. PLoS ONE 19, e0296737 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  195. Bennett, N. R. et al. Atomically accurate de novo design of single-domain antibodies with RFdiffusion. Preprint at bioRxiv https://doi.org/10.1101/2024.03.14.585103 (2025).

  196. Chungyoun, M. & Gray, J. J. AI models for protein design are driving antibody engineering. Curr. Opin. Biomed. Eng. 28, 100473 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Zheng, J., Wang, Y., Liang, Q., Cui, L. & Wang, L. The application of machine learning on antibody discovery and optimization. Molecules 29, 5923 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  198. Desnoyers, L. R. et al. Tumor-specific activation of an EGFR-targeting probody enhances therapeutic index. Sci. Transl. Med. 5, 207ra144 (2013).

    PubMed  Google Scholar 

  199. Chang, H. W. et al. Generating tumor-selective conditionally active biologic anti-CTLA4 antibodies via protein-associated chemical switches. Proc. Natl Acad. Sci. USA 118, e2020606118 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  200. Mimoto, F. et al. Exploitation of elevated extracellular ATP to specifically direct antibody to tumor microenvironment. Cell Rep. 33, 108542 (2020).

    CAS  PubMed  Google Scholar 

  201. Kamata-Sakurai, M. et al. Antibody to CD137 activated by extracellular adenosine triphosphate Is tumor selective and broadly effective in vivo without systemic immune activation. Cancer Discov. 11, 158–175 (2021).

    CAS  PubMed  Google Scholar 

  202. Hironiwa, N. et al. Calcium-dependent antigen binding as a novel modality for antibody recycling by endosomal antigen dissociation. MAbs 8, 65–73 (2016).

    CAS  PubMed  Google Scholar 

  203. Chu, T. H., Patz, E. F. Jr. & Ackerman, M. E. Coming together at the hinges: therapeutic prospects of IgG3. MAbs 13, 1882028 (2021).

    PubMed  PubMed Central  Google Scholar 

  204. Keyt, B. A., Baliga, R., Sinclair, A. M., Carroll, S. F. & Peterson, M. S. Structure, function, and therapeutic use of IgM antibodies. Antibodies 9, 53 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  205. Buchner, J., Sitia, R. & Svilenov, H. L. Understanding IgM structure and biology to engineer new antibody therapeutics. BioDrugs 39, 347–357 (2025).

    PubMed  PubMed Central  Google Scholar 

  206. Bohländer, F. A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases. Front. Immunol. 14, 1127339 (2023).

    PubMed  PubMed Central  Google Scholar 

  207. Candelaria, P. V., Nava, M., Daniels-Wells, T. R. & Penichet, M. L. A fully human IgE specific for CD38 as a potential therapy for multiple myeloma. Cancers 15, 4533 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  208. Chauhan, J. et al. IgE antibodies against cancer: efficacy and safety. Antibodies 9, 55 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  209. Ku, Z. et al. Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants. Nature 595, 718–723 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  210. Marks, L. The birth pangs of monoclonal antibody therapeutics: the failure and legacy of Centoxin. MAbs 4, 403–412 (2012).

    PubMed  PubMed Central  Google Scholar 

  211. de Jong, R. N. et al. A novel platform for the potentiation of therapeutic antibodies based on antigen-dependent formation of IgG hexamers at the cell surface. PLoS Biol. 14, e1002344 (2016). First demonstration of antigen-dependent IgG1 hexamerization (HexaBody technology), which was enabling for several such antibodies that have reached clinical trials.

    PubMed  PubMed Central  Google Scholar 

  212. Grandits, M. et al. Hybrid IgE-IgG1 antibodies (IgEG): a new antibody class that combines IgE and IgG functionality. MAbs 17, 2502673 (2025).

    PubMed  PubMed Central  Google Scholar 

  213. Carter, P. J. & Lazar, G. A. Next generation antibody drugs: pursuit of the ‘high-hanging fruit’. Nat. Rev. Drug Discov. 17, 197–223 (2018).

    CAS  PubMed  Google Scholar 

  214. Lim, S. H., Beers, S. A., Al-Shamkhani, A. & Cragg, M. S. Agonist antibodies for cancer immunotherapy: history, hopes, and challenges. Clin. Cancer Res. 30, 1712–1723 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  215. Jhajj, H. S., Lwo, T. S., Yao, E. L. & Tessier, P. M. Unlocking the potential of agonist antibodies for treating cancer using antibody engineering. Trends Mol. Med. 29, 48–60 (2023).

    CAS  PubMed  Google Scholar 

  216. Yen, M. et al. Facile discovery of surrogate cytokine agonists. Cell 185, 1414–1430.e1419 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  217. Pekar, L., Krah, S. & Zielonka, S. Taming the beast: engineering strategies and biomedical potential of antibody-based cytokine mimetics. Expert Opin. Biol. Ther. 24, 115–118 (2024).

    CAS  PubMed  Google Scholar 

  218. Terstappen, G. C., Meyer, A. H., Bell, R. D. & Zhang, W. Strategies for delivering therapeutics across the blood–brain barrier. Nat. Rev. Drug Discov. 20, 362–383 (2021).

    CAS  PubMed  Google Scholar 

  219. Yu, Y. J. et al. Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target. Sci. Transl. Med. 3, 84ra44 (2011).

    PubMed  Google Scholar 

  220. Grimm, H. P. et al. Delivery of the Brainshuttle amyloid-beta antibody fusion trontinemab to non-human primate brain and projected efficacious dose regimens in humans. MAbs 15, 2261509 (2023).

    PubMed  PubMed Central  Google Scholar 

  221. Okuyama, T. et al. A phase 2/3 trial of pabinafusp alfa, IDS fused with anti-human transferrin receptor antibody, targeting neurodegeneration in MPS-II. Mol. Ther. 29, 671–679 (2021). The fusion protein abinafusp alfa provides the first clinical proof of concept of using transferrin-mediated transcytosis to enhance delivery of a protein therapeutic into the central nervous system.

    CAS  PubMed  Google Scholar 

  222. Deng, B. et al. Oral nanomedicine: challenges and opportunities. Adv. Mater. 36, e2306081 (2024).

    PubMed  Google Scholar 

  223. Nicze, M. et al. The current and promising oral delivery methods for protein- and peptide-based drugs. Int. J. Mol. Sci. 25, 815 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  224. Abramson, A. et al. An ingestible self-orienting system for oral delivery of macromolecules. Science 363, 611–615 (2019). Preclinical proof of concept of oral delivery of a protein therapeutic (insulin) into systemic circulation using a sophisticated ingestible medical device.

    CAS  PubMed  PubMed Central  Google Scholar 

  225. Abramson, A. et al. Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors. Nat. Biotechnol. 40, 103–109 (2022).

    CAS  PubMed  Google Scholar 

  226. Ota, N. et al. Engineering a protease-stable, oral single-domain antibody to inhibit IL-23 signaling. Proc. Natl Acad. Sci. USA 122, e2501635122 (2025).

    CAS  PubMed  Google Scholar 

  227. Harris, C. T. & Cohen, S. Reducing immunogenicity by design: approaches to minimize immunogenicity of monoclonal antibodies. BioDrugs 38, 205–226 (2024).

    CAS  PubMed  PubMed Central  Google Scholar 

  228. Ridker, P. M. et al. Lipid-reduction variability and antidrug-antibody formation with bococizumab. N. Engl. J. Med. 376, 1517–1526 (2017).

    CAS  PubMed  Google Scholar 

  229. Kearns, J. D. et al. A root cause analysis to identify the mechanistic drivers of immunogenicity against the anti-VEGF biotherapeutic brolucizumab. Sci. Transl. Med. 15, eabq5068 (2023).

    CAS  PubMed  Google Scholar 

  230. Dyson, M. R. et al. Beyond affinity: selection of antibody variants with optimal biophysical properties and reduced immunogenicity from mammalian display libraries. MAbs 12, 1829335 (2020). Demonstration that improving the biophysical properties of an antibody (bococizumab) correlates with reduced immunogenicity risk in nonclinical assays.

    PubMed  PubMed Central  Google Scholar 

  231. Schmitt, C. et al. Low immunogenicity of emicizumab in persons with haemophilia A. Haemophilia 27, 984–992 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  232. Sampei, Z. et al. Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PLoS ONE 8, e57479 (2013). Elegant antibody engineering that led to emicizumab, a bispecific antibody (to factor IXa and factor X) with a common light chain approved for treatment of haemophilia A.

    CAS  PubMed  PubMed Central  Google Scholar 

  233. Ghosh, I., Gutka, H., Krause, M. E., Clemens, R. & Kashi, R. S. A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations. MAbs 15, 2205540 (2023).

    PubMed  PubMed Central  Google Scholar 

  234. Dall’Acqua, W. F. et al. Increasing the affinity of a human IgG1 for the neonatal Fc receptor: biological consequences. J. Immunol. 169, 5171–5180 (2002). Antibody engineering that led to the YTE (M252Y:S254T:T256E) triple Fc mutant, which has been used to extend the pharmacokinetic half-life of several approved antibody therapeutics, including nirsevimab, netakimab, amubarvimab and romlusevimab.

    PubMed  Google Scholar 

  235. Gaudinski, M. R. et al. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: a phase 1 open-label clinical trial in healthy adults. PLoS Med. 15, e1002493 (2018).

    PubMed  PubMed Central  Google Scholar 

  236. Robbie, G. J. et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob. Agents Chemother. 57, 6147–6153 (2013). First demonstration of antibody half-life extension in human by using Fc mutants (YTE, M252Y:S254T:T256E).

    CAS  PubMed  PubMed Central  Google Scholar 

  237. Zou, P. Predicting human bioavailability of subcutaneously administered fusion proteins and monoclonal antibodies using human intravenous clearance or antibody isoelectric point. AAPS J. 25, 31 (2023).

    CAS  PubMed  Google Scholar 

  238. Mulvey, A., Trueb, L., Coukos, G. & Arber, C. Novel strategies to manage CAR-T cell toxicity. Nat. Rev. Drug Discov. 24, 379–397 (2025).

    CAS  PubMed  Google Scholar 

  239. Oldham, R. K. Monoclonal antibodies in cancer therapy. J. Clin. Oncol. 1, 582–590 (1983).

    CAS  PubMed  Google Scholar 

  240. Ritz, J. & Schlossman, S. F. Utilization of monoclonal antibodies in the treatment of leukemia and lymphoma. Blood 59, 1–11 (1982).

    CAS  PubMed  Google Scholar 

  241. Saleh, M. N. et al. A phase II trial of murine monoclonal antibody 17-1A and interferon-γ: clinical and immunological data. Cancer Immunol. Immunother. 32, 185–190 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  242. Shawler, D. L., Bartholomew, R. M., Smith, L. M. & Dillman, R. O. Human immune response to multiple injections of murine monoclonal IgG. J. Immunol. 135, 1530–1535 (1985).

    CAS  PubMed  Google Scholar 

  243. Münz, M. et al. Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies. Cancer Cell Int. 10, 44 (2010).

    PubMed  PubMed Central  Google Scholar 

  244. Goodman, G. E., Beaumier, P., Hellström, I., Fernyhough, B. & Hellström, K. E. Pilot trial of murine monoclonal antibodies in patients with advanced melanoma. J. Clin. Oncol. 3, 340–352 (1985).

    CAS  PubMed  Google Scholar 

  245. Vidarsson, G., Dekkers, G. & Rispens, T. IgG subclasses and allotypes: from structure to effector functions. Front. Immunol. 5, 520 (2014).

    PubMed  PubMed Central  Google Scholar 

  246. Ober, R. J., Radu, C. G., Ghetie, V. & Ward, E. S. Differences in promiscuity for antibody–FcRn interactions across species: implications for therapeutic antibodies. Int. Immunol. 13, 1551–1559 (2001).

    CAS  PubMed  Google Scholar 

  247. Foote, J. & Winter, G. Antibody framework residues affecting the conformation of the hypervariable loops. J. Mol. Biol. 224, 487–499 (1992).

    CAS  PubMed  Google Scholar 

  248. Rothe, C. et al. The human combinatorial antibody library HuCAL GOLD combines diversification of all six CDRs according to the natural immune system with a novel display method for efficient selection of high-affinity antibodies. J. Mol. Biol. 376, 1182–1200 (2008).

    CAS  PubMed  Google Scholar 

  249. Hao, Y. et al. Synthetic integrin antibodies discovered by yeast display reveal alphaV subunit pairing preferences with beta subunits. MAbs 16, 2365891 (2024).

    PubMed  PubMed Central  Google Scholar 

  250. Porebski, B. T. et al. Rapid discovery of high-affinity antibodies via massively parallel sequencing, ribosome display and affinity screening. Nat. Biomed. Eng. 8, 214–232 (2024).

    CAS  PubMed  Google Scholar 

  251. Lee, E. C. et al. Complete humanization of the mouse immunoglobulin loci enables efficient therapeutic antibody discovery. Nat. Biotechnol. 32, 356–363 (2014).

    CAS  PubMed  Google Scholar 

  252. Murphy, A. J. et al. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proc. Natl Acad. Sci. USA 111, 5153–5158 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  253. Osborn, M. J. et al. High-affinity IgG antibodies develop naturally in Ig-knockout rats carrying germline human IgH/Igκ/Igλ loci bearing the rat CH region. J. Immunol. 190, 1481–1490 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  254. Ouisse, L. H. et al. Antigen-specific single B cell sorting and expression-cloning from immunoglobulin humanized rats: a rapid and versatile method for the generation of high affinity and discriminative human monoclonal antibodies. BMC Biotechnol. 17, 3 (2017).

    PubMed  PubMed Central  Google Scholar 

  255. Ros, F. et al. Rabbits transgenic for human IgG genes recapitulating rabbit B-cell biology to generate human antibodies of high specificity and affinity. MAbs 12, 1846900 (2020).

    PubMed  PubMed Central  Google Scholar 

  256. Ching, K. H. et al. Chickens with humanized immunoglobulin genes generate antibodies with high affinity and broad epitope coverage to conserved targets. MAbs 10, 71–80 (2018).

    CAS  PubMed  Google Scholar 

  257. Boyd, S. D. & Crowe, J. E. Jr. Deep sequencing and human antibody repertoire analysis. Curr. Opin. Immunol. 40, 103–109 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  258. Kelley, B. The history and potential future of monoclonal antibody therapeutics development and manufacturing in four eras. MAbs 16, 2373330 (2024).

    PubMed  PubMed Central  Google Scholar 

  259. Carter, P. J. Introduction to current and future protein therapeutics: a protein engineering perspective. Exp. Cell. Res. 317, 1261–1269 (2011).

    CAS  PubMed  Google Scholar 

  260. Hummel, J. et al. Modeling the downstream processing of monoclonal antibodies reveals cost advantages for continuous methods for a broad range of manufacturing scales. Biotechnol. J. 14, e1700665 (2018).

    PubMed  Google Scholar 

  261. Barnard, G. C., Zhou, M., Shen, A., Yuk, I. H. & Laird, M. W. Utilizing targeted integration CHO pools to potentially accelerate the GMP manufacturing of monoclonal and bispecific antibodies. Biotechnol. Prog. 40, e3399 (2024).

    CAS  PubMed  Google Scholar 

  262. Glinšek, K., Bozovičar, K. & Bratkovič, T. CRISPR technologies in Chinese hamster ovary cell line engineering. Int. J. Mol. Sci. 24, 8144 (2023).

    PubMed  PubMed Central  Google Scholar 

  263. Ritacco, F. V., Wu, Y. & Khetan, A. Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: history, key components, and optimization strategies. Biotechnol. Prog. 34, 1407–1426 (2018).

    CAS  PubMed  Google Scholar 

  264. Xu, W. J., Lin, Y., Mi, C. L., Pang, J. Y. & Wang, T. Y. Progress in fed-batch culture for recombinant protein production in CHO cells. Appl. Microbiol. Biotechnol. 107, 1063–1075 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  265. MacDonald, M. A. et al. Perfusion culture of Chinese hamster ovary cells for bioprocessing applications. Crit. Rev. Biotechnol. 42, 1099–1115 (2022).

    CAS  PubMed  Google Scholar 

  266. Kumar, A., Udugama, I. A., Gargalo, C. L. & Gernaey, K. V. Why Is batch processing still dominating the biologics landscape? Towards an integrated continuous bioprocessing alternative. Processes 8, 1641 (2020).

    Google Scholar 

  267. Dorival-García, N. et al. Large-scale assessment of extractables and leachables in single-use bags for biomanufacturing. Anal. Chem. 90, 9006–9015 (2018).

    PubMed  Google Scholar 

  268. Amasawa, E., Kuroda, H., Okamura, K., Badr, S. & Sugiyama, H. Cost–benefit analysis of monoclonal antibody cultivation scenarios in terms of life cycle environmental impact and operating cost. ACS Sustain. Chem. Eng. 9, 14012–14021 (2021).

    CAS  Google Scholar 

  269. Samaras, J. J., Micheletti, M. & Ding, W. Transformation of biopharmaceutical manufacturing through single-use technologies: current state, remaining challenges, and future development. Annu. Rev. Chem. Biomol. Eng. 13, 73–97 (2022).

    PubMed  Google Scholar 

Read the whole story
sarcozona
15 hours ago
reply
Happy anniversary!
Epiphyte City
Share this story
Delete

Multiple Men Have Impersonated ICE Agents To Kidnap And Assault Women

1 Share
Read the whole story
sarcozona
17 hours ago
reply
Epiphyte City
Share this story
Delete

The entities enabling scientific fraud at scale are large, resilient, and growing rapidly

1 Share
Read the whole story
sarcozona
1 day ago
reply
Epiphyte City
Share this story
Delete
Next Page of Stories