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Köhler, G. & Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495–497 (1975). Ground-breaking invention of hybridoma know-how that was a key step in the direction of this contemporary period of antibody-based therapeutics.
Bradbury, A. & Plückthun, A. Reproducibility: standardize antibodies utilized in analysis. Nature 518, 27–29 (2015).
Uhr, J. W. The 1984 Nobel Prize in Medicine. Science 226, 1025–1028 (1984).
Boulianne, G. L., Hozumi, N. & Shulman, M. J. Production of practical chimaeric mouse/human antibody. Nature 312, 643–646 (1984). Together with ref. 5 is the primary demonstration of chimerization of a murine monoclonal antibody.
Morrison, S. L., Johnson, M. J., Herzenberg, L. A. & Oi, V. T. Chimeric human antibody molecules: mouse antigen-binding domains with human fixed area domains. Proc. Natl Acad. Sci. USA 81, 6851–6855 (1984). Together with ref. 4 is the primary demonstration of chimerization of a murine monoclonal antibody.
Jones, P. T., Dear, P. H., Foote, J., Neuberger, M. S. & Winter, G. Replacing the complementarity-determining areas in a human antibody with these from a mouse. Nature 321, 522–525 (1986). First demonstration of humanization of a murine antibody that, along with refs. 7 and eight, ultimately led to a minimum of 105 accredited humanized antibody therapeutics.
Riechmann, L., Clark, M., Waldmann, H. & Winter, G. Reshaping human antibodies for remedy. Nature 332, 323–327 (1988).
Verhoeyen, M., Milstein, C. & Winter, G. Reshaping human antibodies: grafting an antilysozyme exercise. Science 239, 1534–1536 (1988).
Wilkinson, I. & Hale, G. Systematic evaluation of the numerous designs of 819 therapeutic antibodies and Fc fusion proteins assigned worldwide nonproprietary names. MAbs 14, 2123299 (2022).
Carter, P. J. & Rajpal, A. Designing antibodies as therapeutics. Cell 185, 2789–2805 (2022).
Paul, S. et al. Cancer remedy with antibodies. Nat. Rev. Cancer 24, 399–426 (2024).
Carter, P. J. & Quarmby, V. Immunogenicity danger evaluation and mitigation for engineered antibody and protein therapeutics. Nat. Rev. Drug Discov. 23, 898–913 (2024).
Qian, L. et al. The daybreak of a brand new period: concentrating on the “undruggables” with antibody-based therapeutics. Chem. Rev. 123, 7782–7853 (2023).
Brown, D. G., Wobst, H. J., Kapoor, A., Kenna, L. A. & Southall, N. Clinical growth occasions for progressive medicine. Nat. Rev. Drug Discov. 21, 793–794 (2022).
Genetta, T. B. & Mauro, V. F. ABCIXIMAB: a brand new antiaggregant utilized in angioplasty. Ann. Pharmacother. 30, 251–257 (1996).
Vincenti, F. Daclizumab: novel biologic immunoprophylaxis for prevention of acute rejection in renal transplantation. Transplant. Proc. 31, 2206–2207 (1999).
Bain, B. & Brazil, M. Adalimumab. Nat. Rev. Drug Discov. 2, 693–694 (2003).
US Food and Drug Administration. Prescribing info, HUMIRA® (adalimumab) injection, for subcutaneous use. fda.gov (2023).
Gibbons, J. B., Laber, M. & Bennett, C. L. Humira: the primary $20 billion drug. Am. J. Manag. Care 29, 78–80 (2023).
Crescioli, S. et al. Antibodies to look at in 2025. MAbs 17, 2443538 (2025). Most current of a daily sequence of articles reviewing lately accredited and registrational stage antibody therapeutics.
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).
Goebeler, M. E., Stuhler, G. & Bargou, R. Bispecific and multispecific antibodies in oncology: alternatives and challenges. Nat. Rev. Clin. Oncol. 21, 539–560 (2024).
Klein, C., Brinkmann, U., Reichert, J. M. & Kontermann, R. E. The current and way forward for bispecific antibodies for most cancers remedy. Nat. Rev. Drug Discov. 23, 301–319 (2024).
Pirkalkhoran, S. et al. Bioengineering of antibody fragments: challenges and alternatives. Bioengineering 10, 122 (2023).
Silver, A. B., Leonard, E. Okay., Gould, J. R. & Spangler, J. B. Engineered antibody fusion proteins for focused illness remedy. Trends Pharmacol. Sci. 42, 1064–1081 (2021).
Larbouret, C., Gros, L., Pèlegrin, A. & Chardès, T. Improving biologics’ effectiveness in medical oncology: from the mix of two monoclonal antibodies to oligoclonal antibody mixtures. Cancers 13, 4620 (2021).
Cappell, Okay. M. & Kochenderfer, J. N. Long-term outcomes following CAR T cell remedy: what we all know to date. Nat. Rev. Clin. Oncol. 20, 359–371 (2023).
Moolten, F. L. & Cooperband, S. R. Selective destruction of goal cells by diphtheria toxin conjugated to antibody directed in opposition to antigens on the cells. Science 169, 68–70 (1970). First demonstration of an immunotoxin for directed killing of goal cells.
Casi, G. & Neri, D. Antibody-drug conjugates and small molecule-drug conjugates: alternatives and challenges for the event of selective anticancer cytotoxic brokers. J. Med. Chem. 58, 8751–8761 (2015).
Sedalacek, H.-H. et al. (eds) Antibodies as Carriers of Cytotoxicity. Contributions to Oncology Vol. 43 (eds Huber, P & Queisser, W.) (Karger, 1992).
Mahalingaiah, P. Okay. et al. Potential mechanisms of target-independent uptake and toxicity of antibody-drug conjugates. Pharmacol. Ther. 200, 110–125 (2019).
Doronina, S. O. et al. Enhanced exercise of monomethylauristatin F by monoclonal antibody supply: results of linker know-how on efficacy and toxicity. Bioconjug. Chem. 17, 114–124 (2006).
Doronina, S. O. et al. Development of potent monoclonal antibody auristatin conjugates for most cancers remedy. Nat. Biotechnol. 21, 778–784 (2003). First publication of ADCs with auristatin payloads, which has led to the approval of a minimum of 9 such ADCs.
Bross, P. F. et al. Approval abstract: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin. Cancer Res. 7, 1490–1496 (2001).
Norsworthy, Okay. J. et al. FDA approval abstract: mylotarg for therapy of sufferers with relapsed or refractory CD33-positive acute myeloid leukemia. Oncologist 23, 1103–1108 (2018).
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).
Lehar, S. M. et al. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature 527, 323–328 (2015).
Dragovich, P. S. Degrader-antibody conjugates. Chem. Soc. Rev. 51, 3886–3897 (2022).
Poudel, Y. B., Thakore, R. R. & Chekler, E. P. The new frontier: merging molecular glue degrader and antibody-drug conjugate modalities to beat strategic challenges. J. Med. Chem. 67, 15996–16001 (2024).
Nisonoff, A., Wissler, F. C. & Lipman, L. N. Properties of the foremost element of a peptic digest of rabbit antibody. Science 132, 1770–1771 (1960). First demonstration of the idea of bispecific antibodies.
Seimetz, D., Lindhofer, H. & Bokemeyer, C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a focused most cancers immunotherapy. Cancer Treat. Rev. 36, 458–467 (2010). First accredited bispecific: catumaxomab (concentrating on EpCAM and CD3; TCE).
Milstein, C. & Cuello, A. C. Hybrid hybridomas and their use in immunohistochemistry. Nature 305, 537–540 (1983).
Staerz, U. D., Kanagawa, O. & Bevan, M. J. Hybrid antibodies can goal websites for assault by T cells. Nature 314, 628–631 (1985). First demonstration of the idea of utilizing bispecific antibodies to direct the killing of tumour cells by T cells, resulting in a minimum of 9 such accredited TCEs.
Underwood, D. J., Bettencourt, J. & Jawad, Z. The manufacturing concerns of bispecific antibodies. Expert Opin. Biol. Ther. 22, 1043–1065 (2022).
Brinkmann, U. & Kontermann, R. E. The making of bispecific antibodies. MAbs 9, 182–212 (2017).
Spiess, C., Zhai, Q. & Carter, P. J. Alternative molecular codecs and therapeutic purposes for bispecific antibodies. Mol. Immunol. 67, 95–106 (2015).
Mack, M., Riethmüller, G. & Kufer, P. A small bispecific antibody assemble expressed as a practical single-chain molecule with excessive 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 ultimately led to blinatumomab.
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’ know-how that after refinement (ref. 49 and ref. 52), has been broadly used for Fc heterodimerization, together with for a minimum of three accredited bispecific antibodies: mosunetuzumab, glofitamab-gxbm and faricimab-svoa.
Atwell, S., Ridgway, J. B., Wells, J. A. & Carter, P. Stable heterodimers from transforming the area interface of a homodimer utilizing a phage show library. J. Mol. Biol. 270, 26–35 (1997).
Schaefer, W. et al. Immunoglobulin area crossover as a generic strategy for the manufacturing of bispecific IgG antibodies. Proc. Natl Acad. Sci. USA 108, 11187–11192 (2011). First demonstration of CrossMab know-how that has been used to generate a minimum of two accredited bispecific antibodies: glofitamab-gxbm and faricimab-svoa.
Surowka, M., Schaefer, W. & Klein, C. Ten years within the making: software of CrossMab know-how for the event of therapeutic bispecific antibodies and antibody fusion proteins. MAbs 13, 1967714 (2021).
Merchant, A. M. et al. An environment friendly path to human bispecific IgG. Nat. Biotechnol. 16, 677–681 (1998). First use of widespread mild chains, a know-how subsequently used for a minimum of 4 accredited bispecific antibodies: emicizumab, odronextamab, zenocutuzumab-zbco and linvoseltamab.
Labrijn, A. F. et al. Efficient technology of steady bispecific IgG1 by managed Fab-arm change. Proc. Natl Acad. Sci. USA 110, 5145–5150 (2013). First demonstration of DuoBody know-how that has been used for a minimum of 4 accredited bispecific antibodies: amivantamab-vmjw, epcoritamab-bysp, talquetamab-tgvs and teclistamab-cqyv.
Von Kreudenstein, T. S. et al. Improving biophysical properties of a bispecific antibody scaffold to help developability: high quality by molecular design. MAbs 5, 646–654 (2013).
Yao, Y., Hu, Y. & Wang, F. Trispecific antibodies for most cancers immunotherapy. Immunol. Rev. 169, 389–399 (2023).
Cheson, B. D. & Leonard, J. P. Monoclonal antibody remedy for B-cell non-Hodgkin’s lymphoma. N. Engl. J. Med. 359, 613–626 (2008).
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).
Alduaij, W. et al. Novel kind II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell loss of life in B-cell malignancies. Blood 117, 4519–4529 (2011).
Ghosh, A. et al. Decoding the molecular interaction of CD20 and therapeutic antibodies with quick volumetric nanoscopy. Science 387, eadq4510 (2025).
Weng, W. Okay. & Levy, R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in sufferers with follicular lymphoma. J. Clin. Oncol. 21, 3940–3947 (2003).
Cartron, G. et al. Therapeutic exercise of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 99, 754–758 (2002). First demonstration of the medical exercise of an antibody (rituximab) correlating with polymorphisms in an Fcγ receptor (FcγRIIIA).
Mossner, E. et al. Increasing the efficacy of CD20 antibody remedy by the engineering of a brand new kind II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 115, 4393–4402 (2010).
Cheson, B. D. et al. Overall survival profit in sufferers with rituximab-refractory indolent non-Hodgkin lymphoma who obtained obinutuzumab plus bendamustine induction and obinutuzumab upkeep within the GADOLIN research. J. Clin. Oncol. 36, 2259–2266 (2018).
Goede, V. et al. Obinutuzumab plus chlorambucil in sufferers with CLL and coexisting circumstances. N. Engl. J. Med. 370, 1101–1110 (2014).
Townsend, W. et al. Obinutuzumab versus rituximab immunochemotherapy in beforehand untreated iNHL: last outcomes from the GALLIUM research. Hemasphere 7, e919 (2023).
Vitolo, U. et al. Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in beforehand untreated diffuse giant B-cell lymphoma. J. Clin. Oncol. 35, 3529–3537 (2017).
Davies, A. et al. Obinutuzumab within the therapy of B-cell malignancies: a complete evaluate. Future Oncol. 18, 2943–2966 (2022).
Marcus, R. et al. Obinutuzumab for the first-line therapy of follicular lymphoma. N. Engl. J. Med. 377, 1331–1344 (2017).
Lazar, G. A. et al. Engineered antibody Fc variants with enhanced effector operate. Proc. Natl Acad. Sci. USA 103, 4005–4010 (2006). Extensive mutational evaluation of IgG1 Fc to tailor effector capabilities.
Salles, G. et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse giant B-cell lymphoma (L-MIND): a multicentre, potential, single-arm, section 2 research. Lancet Oncol. 21, 978–988 (2020).
Duell, J. et al. Tafasitamab for sufferers with relapsed or refractory diffuse giant B-cell lymphoma: last 5-year efficacy and security findings within the section II L-MIND research. Haematologica 109, 553–566 (2024).
Hiraga, J. et al. Down-regulation of CD20 expression in B-cell lymphoma cells after therapy with rituximab-containing mixture chemotherapies: its prevalence and medical significance. Blood 113, 4885–4893 (2009).
Rehman, R. U., Anjum, A. F. & Fatima, R. Tarlatamab and the way forward for immunotherapy: a brand new strategy to small cell lung most cancers. Curr. Ther. Res. Clin. Exp. 102, 100773 (2025).
Kantarjian, H. et al. Blinatumomab versus chemotherapy for superior acute lymphoblastic leukemia. N. Engl. J. Med. 376, 836–847 (2017).
Löffler, A. et al. A recombinant bispecific single-chain antibody, CD19 × CD3, induces fast and excessive lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood 95, 2098–2103 (2000).
Mocquot, P., Mossazadeh, Y., Lapierre, L., Pineau, F. & Despas, F. The pharmacology of blinatumomab: state-of-the-art on pharmacodynamics, pharmacokinetics, adversarial drug reactions and analysis in medical trials. J. Clin. Pharm. Ther. 47, 1337–1351 (2022).
Elmeliegy, M. et al. Dosing methods and quantitative medical pharmacology for bispecific T-cell engagers growth in oncology. Clin. Pharmacol. Ther. 116, 637–646 (2024).
Budde, L. E. et al. Durable responses with mosunetuzumab in relapsed/refractory indolent and aggressive B-cell non-Hodgkin lymphomas: prolonged follow-up of a section I/II research. J. Clin. Oncol. 42, 2250–2256 (2024).
Dickinson, M. J. et al. Glofitamab for relapsed or refractory diffuse giant B-cell lymphoma. N. Engl. J. Med. 387, 2220–2231 (2022).
Thieblemont, C. et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory giant B-cell lymphoma: dose enlargement in a section I/II trial. J. Clin. Oncol. 41, 2238–2247 (2023).
Kim, T. M. et al. Safety and efficacy of odronextamab in sufferers with relapsed or refractory follicular lymphoma. Ann. Oncol. 35, 1039–1047 (2024).
Moreau, P. et al. Teclistamab in relapsed or refractory a number of myeloma. N. Engl. J. Med. 387, 495–505 (2022).
Lesokhin, A. M. et al. Elranatamab in relapsed or refractory a number of myeloma: section 2 MagnetisMM-3 trial outcomes. Nat. Med. 29, 2259–2267 (2023).
Avigan, Z. M., Rattu, M. A. & Richter, J. An analysis of linvoseltamab for therapy of relapsed/refractory a number of myeloma. Expert Opin. Biol. Ther. 25, 221–228 (2025).
Chari, A. et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for a number of myeloma. N. Engl. J. Med. 387, 2232–2244 (2022).
Bacac, M. et al. CD20-TCB with obinutuzumab pretreatment as next-generation therapy of hematologic malignancies. Clin. Cancer Res. 24, 4785–4797 (2018).
Guedan, S., Ruella, M. & June, C. H. Emerging mobile therapies for most cancers. Annu. Rev. Immunol. 37, 145–171 (2019).
Haydu, J. E. & Abramson, J. S. The guidelines of T-cell engagement: present state of CAR T cells and bispecific antibodies in B-cell lymphomas. Blood Adv. 8, 4700–4710 (2024).
Swan, D., Madduri, D. & Hocking, J. CAR-T cell remedy in a number of myeloma: present standing and future challenges. Blood Cancer J. 14, 206 (2024).
Anderson, N. D. et al. Transcriptional signatures related to persisting CD19 CAR-T cells in kids with leukemia. Nat. Med. 29, 1700–1709 (2023).
Witzig, T. E. et al. Randomized managed trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for sufferers with relapsed or refractory low-grade, follicular, or reworked B-cell non-Hodgkin’s lymphoma. J. Clin. Oncol. 20, 2453–2463 (2002).
Horning, S. J. et al. Efficacy and security of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J. Clin. Oncol. 23, 712–719 (2005).
Kantarjian, H. M. et al. Inotuzumab ozogamicin versus customary remedy for acute lymphoblastic leukemia. N. Engl. J. Med. 375, 740–753 (2016).
Tilly, H. et al. Polatuzumab vedotin in beforehand untreated diffuse giant B-cell lymphoma. N. Engl. J. Med. 386, 351–363 (2022).
Caimi, P. F. et al. Loncastuximab tesirine in relapsed or refractory diffuse giant B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, section 2 trial. Lancet Oncol. 22, 790–800 (2021).
Tai, Y. T. et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of a number of myeloma. Blood 123, 3128–3138 (2014).
Dimopoulos, M. A. et al. Efficacy and security of single-agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in sufferers with relapsed or refractory a number of myeloma (DREAMM-3): a section 3, open-label, randomised research. Lancet Haematol. 10, e801–e812 (2023).
Kreitman, R. J. et al. Moxetumomab pasudotox in relapsed/refractory bushy cell leukemia. Leukemia 32, 1768–1777 (2018).
Khoury, R. et al. Mechanisms of resistance to antibody-drug conjugates. Int. J. Mol. Sci. 24, 9674 (2023).
Edwards, J. C. et al. Efficacy of B-cell-targeted remedy with rituximab in sufferers 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 sufferers with rheumatoid arthritis.
Cohen, S. B. et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis issue remedy: outcomes of a multicenter, randomized, double-blind, placebo-controlled, section III trial evaluating major efficacy and security at twenty-four weeks. Arthritis Rheum. 54, 2793–2806 (2006).
Joly, P. et al. First-line rituximab mixed with short-term prednisone versus prednisone alone for the therapy of pemphigus (Ritux 3): a potential, multicentre, parallel-group, open-label randomised trial. Lancet 389, 2031–2040 (2017).
Jones, R. B. et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N. Engl. J. Med. 363, 211–220 (2010).
Martin, F. & Chan, A. C. B cell immunobiology in illness: evolving ideas from the clinic. Annu. Rev. Immunol. 24, 467–496 (2006).
Merrill, J. T. et al. Efficacy and security of rituximab in moderately-to-severely energetic systemic lupus erythematosus: the randomized, double-blind, section II/III systemic lupus erythematosus analysis of rituximab trial. Arthritis Rheum. 62, 222–233 (2010).
Rovin, B. H. et al. Efficacy and security of rituximab in sufferers with energetic proliferative lupus nephritis: the lupus nephritis evaluation with rituximab research. Arthritis Rheum. 64, 1215–1226 (2012).
Gomez Mendez, L. M. et al. Peripheral blood B cell depletion after rituximab and full response in lupus nephritis. Clin. J. Am. Soc. Nephrol. 13, 1502–1509 (2018).
Gong, Q. et al. Importance of mobile microenvironment and circulatory dynamics in B cell immunotherapy. J. Immunol. 174, 817–826 (2005).
Ahuja, A. et al. Depletion of B cells in murine lupus: efficacy and resistance. J. Immunol. 179, 3351–3361 (2007).
Marinov, A. D. et al. The kind II anti-CD20 antibody obinutuzumab (GA101) is simpler than rituximab at depleting B cells and treating illness in a murine lupus mannequin. Arthritis Rheumatol. 73, 826–836 (2021).
Furie, R. A. et al. Efficacy and security of obinutuzumab in energetic lupus nephritis. N. Engl. J. Med. 392, 1471–1483 (2025).
Hauser, S. L. et al. B-cell depletion with rituximab in relapsing-remitting a number of sclerosis. N. Engl. J. Med. 358, 676–688 (2008).
Hawker, Okay. et al. Rituximab in sufferers with major progressive a number of sclerosis: outcomes of a randomized double-blind placebo-controlled multicenter trial. Ann. Neurol. 66, 460–471 (2009).
Dunn, N. et al. Rituximab in a number of sclerosis: frequency and medical relevance of anti-drug antibodies. Mult. Scler. 24, 1224–1233 (2018).
Wolf, A. B. et al. Rituximab-induced serum illness in a number of sclerosis sufferers. Mult. Scler. Relat. Disord. 36, 101402 (2019).
Wincup, C. et al. Anti-rituximab antibodies reveal neutralizing capability, affiliate with decrease circulating drug ranges and earlier relapse in lupus. Rheumatology 62, 2601–2610 (2023).
Hauser, S. L. et al. Ofatumumab versus teriflunomide in a number of sclerosis. N. Engl. J. Med. 383, 546–557 (2020).
Hauser, S. L. et al. Ocrelizumab versus interferon beta-1a in relapsing a number of sclerosis. N. Engl. J. Med. 376, 221–234 (2017). First section III demonstration of efficacy of ocrelizumab, a humanized anti-CD20 antibody, in contrast with interferon β1a customary of care in relapsing a number of sclerosis.
Montalban, X. et al. Ocrelizumab versus placebo in major progressive a number of sclerosis. N. Engl. J. Med. 376, 209–220 (2017). First section III demonstration of efficacy of ocrelizumab, a humanized anti-CD20 antibody, in PPMS.
Fischbach, F. et al. CD19-targeted chimeric antigen receptor T cell remedy in two sufferers with a number of sclerosis. Med 5, 550–558 e552 (2024).
Müller, F. et al. CD19 CAR T-cell remedy in autoimmune illness – a case sequence with follow-up. N. Engl. J. Med. 390, 687–700 (2024).
Swain, S. M., Shastry, M. & Hamilton, E. Targeting HER2-positive breast most cancers: advances and future instructions. Nat. Rev. Drug Discov. 22, 101–126 (2023).
Carter, P. et al. Humanization of an anti-p185HER2 antibody for human most cancers remedy. Proc. Natl Acad. Sci. USA 89, 4285–4289 (1992). Humanization of a murine anti-HER2 antibody, 4D5, that led to trastuzumab, the primary antibody to be accredited for breast most cancers.
Hudziak, R. M. et al. p185HER2 monoclonal antibody has antiproliferative results in vitro and sensitizes human breast tumor cells to tumor necrosis issue. Mol. Cell. Biol. 9, 1165–1172 (1989).
Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody in opposition to HER2 for metastatic breast most cancers that overexpresses HER2. N. Engl. J. Med. 344, 783–792 (2001). Demonstration that the humanized anti-HER2 antibody trastuzumab will increase the medical advantage of chemotherapy in metastatic breast most cancers that overexpresses HER2.
Jorgensen, J. T. et al. A companion diagnostic with important medical influence in therapy of breast and gastric most cancers. Front. Oncol. 11, 676939 (2021).
Slamon, D. et al. Adjuvant trastuzumab in HER2-positive breast most cancers. N. Engl. J. Med. 365, 1273–1283 (2011).
Agus, D. B. et al. Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor development. Cancer Cell 2, 127–137 (2002).
Shao, Z. et al. Efficacy, security, and tolerability of pertuzumab, trastuzumab, and docetaxel for sufferers with early or domestically superior ERBB2-positive breast most cancers in Asia: the PEONY section 3 randomized medical trial. JAMA Oncol. 6, e193692 (2020).
von Minckwitz, G. et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast most cancers. N. Engl. J. Med. 377, 122–131 (2017).
Swain, S. M. et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast most cancers. N. Engl. J. Med. 372, 724–734 (2015).
Gao, J. J. et al. FDA approval abstract: pertuzumab, trastuzumab, and hyaluronidase-zzxf injection for subcutaneous use in sufferers with HER2-positive breast most cancers. Clin. Cancer Res. 27, 2126–2129 (2021).
Hurvitz, S. A. et al. Analysis of Fcγ receptor IIIa and IIa polymorphisms: lack of correlation with end result in trastuzumab-treated breast most cancers sufferers. Clin. Cancer Res. 18, 3478–3486 (2012).
Tamura, Okay. et al. FcγR2A and 3A polymorphisms predict medical end result of trastuzumab in each neoadjuvant and metastatic settings in sufferers with HER2-positive breast most cancers. Ann. Oncol. 22, 1302–1307 (2011).
Wang, D. S. et al. FcγRIIA and IIIA polymorphisms predict medical end result of trastuzumab-treated metastatic gastric most cancers. OncoTargets Ther. 10, 5065–5076 (2017).
Nordstrom, J. L. et al. Anti-tumor exercise and toxicokinetics evaluation of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcγ receptor binding properties. Breast Cancer Res. 13, R123 (2011).
Fendly, B. M. et al. Characterization of murine monoclonal antibodies reactive to both the human epidermal development issue receptor or HER2/neu gene product. Cancer Res. 50, 1550–1558 (1990).
Rugo, H. S. et al. Efficacy of margetuximab vs trastuzumab in sufferers with pretreated ERBB2-positive superior breast most cancers: a section 3 randomized medical trial. JAMA Oncol. 7, 573–584 (2021).
Lewis Phillips, G. D. et al. Targeting HER2-positive breast most cancers with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 68, 9280–9290 (2008).
Verma, S. et al. Trastuzumab emtansine for HER2-positive superior breast most cancers. N. Engl. J. Med. 367, 1783–1791 (2012).
von Minckwitz, G. et al. Trastuzumab emtansine for residual invasive HER2-positive breast most cancers. N. Engl. J. Med. 380, 617–628 (2019).
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).
Ogitani, Y., Hagihara, Okay., Oitate, M., Naito, H. & Agatsuma, T. Bystander killing impact of DS-8201a, a novel anti-human epidermal development issue receptor 2 antibody-drug conjugate, in tumors with human epidermal development issue receptor 2 heterogeneity. Cancer Sci. 107, 1039–1046 (2016).
Narayan, P. et al. FDA approval abstract: fam-trastuzumab deruxtecan-nxki for the therapy of unresectable or metastatic HER2-positive breast most cancers. Clin. Cancer Res. 27, 4478–4485 (2021).
Modi, S. et al. Trastuzumab deruxtecan in beforehand handled HER2-positive breast most cancers. N. Engl. J. Med. 382, 610–621 (2020).
Modi, S. et al. Trastuzumab deruxtecan in beforehand handled HER2-low superior breast most cancers. N. Engl. J. Med. 387, 9–20 (2022). Landmark medical research demonstrating the efficacy of the ADC, trastuzumab deruxtecan, in beforehand handled HER2-low breast most cancers.
Prescribing info, ENHERTU® (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use. fda.gov (2025).
Weisser, N. E. et al. An anti-HER2 biparatopic antibody that induces distinctive HER2 clustering and complement-dependent cytotoxicity. Nat. Commun. 14, 1394 (2023).
Harding, J. J. et al. Zanidatamab for HER2-amplified, unresectable, domestically superior or metastatic biliary tract most cancers (HERIZON-BTC-01): a multicentre, single-arm, section 2b research. Lancet Oncol. 24, 772–782 (2023).
Keam, S. J. Zanidatamab: first approval. Drugs 85, 707–714 (2025).
Jonna, S. et al. Detection of NRG1 gene fusions in stable tumors. Clin. Cancer Res. 25, 4966–4972 (2019).
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).
Schram, A. M. et al. Efficacy of zenocutuzumab in NRG1 fusion-positive most cancers. N. Engl. J. Med. 392, 566–576 (2025).
Press, M. F., Cordon-Cardo, C. & Slamon, D. J. Expression of the HER-2/neu proto-oncogene in regular human grownup and fetal tissues. Oncogene 5, 953–962 (1990).
Gordon, L. I. et al. Blockade of the erbB2 receptor induces cardiomyocyte loss of life by mitochondrial and reactive oxygen species-dependent pathways. J. Biol. Chem. 284, 2080–2087 (2009).
Seidman, A. et al. Cardiac dysfunction within the trastuzumab medical trials expertise. J. Clin. Oncol. 20, 1215–1221 (2002).
Morgan, R. A. et al. Case report of a critical adversarial occasion following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol. Ther. 18, 843–851 (2010).
Slaga, D. et al. Avidity-based binding to HER2 leads to 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 boost the selectivity of cytotoxicity in the direction of tumour cells overexpressing HER2.
Oostindie, S. C. et al. Logic-gated antibody pairs that selectively act on cells co-expressing two antigens. Nat. Biotechnol. 40, 1509–1519 (2022).
Davis, J. D. et al. Subcutaneous administration of monoclonal antibodies: pharmacology, supply, immunogenicity, and learnings from purposes to medical growth. Clin. Pharmacol. Ther. 115, 422–439 (2024).
Lang, J. J. et al. Patient-reported disruptions to most cancers care throughout the COVID-19 pandemic: a nationwide cross-sectional research. Cancer Med. 12, 4773–4785 (2023).
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).
Prescribing info, Soliris (eculizumab) for intravenous infusion. fda.gov (2025).
Sheridan, D. et al. Design and preclinical characterization of ALXN1210: a novel anti-C5 antibody with prolonged length of motion. PLoS ONE 13, e0195909 (2018).
Zalevsky, J. et al. Enhanced antibody half-life improves in vivo exercise. Nat. Biotechnol. 28, 157–159 (2010).
Prescribing info, Ultomiris (ravulizumab-cwvz) injection, for intravenous use. fda.gov (2024).
Viola, M. et al. Subcutaneous supply of monoclonal antibodies: how can we get there? J. Control. Release 286, 301–314 (2018).
Strickley, R. G. & Lambert, W. J. A evaluate of formulations of commercially out there antibodies. J. Pharm. Sci. 110, 2590–2608 e2556 (2021).
Zarzar, J. et al. High focus formulation developability approaches and concerns. MAbs 15, 2211185 (2023).
Sánchez-Félix, M., Burke, M., Chen, H. H., Patterson, C. & Mittal, S. Predicting bioavailability of monoclonal antibodies after subcutaneous administration: open innovation problem. Adv. Drug Deliv. Rev. 167, 66–77 (2020).
Sauna, Z. E., Jawa, V., Balu-Iyer, S. & Chirmule, N. Understanding preclinical and medical immunogenicity dangers in novel biotherapeutics growth. Front. Immunol. 14, 1151888 (2023).
Swanson, S. J. What are clinically important anti-drug antibodies and why is it necessary to establish them. Front. Immunol. 15, 1401178 (2024).
Homšek, A. et al. Pharmacokinetic characterization, advantages and boundaries of subcutaneous administration of monoclonal antibodies in oncology. J. Oncol. Pharm. Pract. 29, 431–440 (2022).
Dai, J. et al. Variable area mutational evaluation to probe the molecular mechanisms of excessive viscosity of an IgG1 antibody. MAbs 16, 2304282 (2024).
Nichols, P. et al. Rational design of viscosity lowering mutants of a monoclonal antibody: hydrophobic versus electrostatic inter-molecular interactions. MAbs 7, 212–230 (2015).
Yadav, S. et al. Establishing a hyperlink between amino acid sequences and self-associating and viscoelastic conduct of two intently associated monoclonal antibodies. Pharm. Res. 28, 1750–1764 (2011).
Heisler, J., Kovner, D., Izadi, S., Zarzar, J. & Carter, P. J. Modulation of the excessive focus viscosity of IgG1 antibodies utilizing clinically validated Fc mutations. MAbs 16, 2379560 (2024).
Igawa, T., Haraya, Okay. & Hattori, Okay. Sweeping antibody as a novel therapeutic antibody modality able to eliminating soluble antigens from circulation. Immunol. Rev. 270, 132–151 (2016).
Igawa, T. et al. Engineered monoclonal antibody with novel antigen-sweeping exercise in vivo. PLoS ONE 8, e63236 (2013).
Igawa, T. et al. Antibody recycling by engineered pH-dependent antigen binding improves the length of antigen neutralization. Nat. Biotechnol. 28, 1203–1207 (2010). First demonstration that engineering an antibody for pH-dependent antigen binding might prolong its plasma life and length of antigen neutralization in vivo.
Sampei, Z. et al. Antibody engineering to generate SKY59, a long-acting anti-C5 recycling antibody. PLoS ONE 13, e0209509 (2018).
Fukuzawa, T. et al. Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a possible remedy for complement-mediated illnesses. Sci. Rep. 7, 1080 (2017).
Callaway, E. Chemistry Nobel goes to builders of AlphaFold AI that predicts protein buildings. Nature 634, 525–526 (2024).
Jumper, J. et al. Highly correct protein construction prediction with AlphaFold. Nature 596, 583–589 (2021). First launch of AlphaFold, a synthetic intelligence software that predicts protein buildings from amino acid sequences with beforehand unprecedented pace and accuracy, with nice potential to speed up fundamental analysis and drug discovery.
Vazquez Torres, S. et al. De novo design of high-affinity binders of bioactive helical peptides. Nature 626, 435–442 (2024).
Ichikawa, D. M. et al. A common deep-learning mannequin for zinc finger design allows transcription issue reprogramming. Nat. Biotechnol. 41, 1117–1129 (2023).
Hie, B. L. et al. Efficient evolution of human antibodies from basic protein language fashions. Nat. Biotechnol. 42, 275–283 (2024).
Frey, N. C. et al. Lab-in-the-loop therapeutic antibody design with deep studying. Preprint at bioRxiv (2025).
Li, L. et al. Machine studying optimization of candidate antibody yields extremely various sub-nanomolar affinity antibody libraries. Nat. Commun. 14, 3454 (2023).
Harvey, E. P. et al. An in silico methodology to evaluate antibody fragment polyreactivity. Nat. Commun. 13, 7554 (2022).
Sweet-Jones, J. & Martin, A. C. R. An antibody developability triaging pipeline exploiting protein language fashions. MAbs 17, 2472009 (2025).
Kalejaye, L. A. et al. Accelerating high-concentration monoclonal antibody growth with large-scale viscosity knowledge and ensemble deep studying. MAbs 17, 2483944 (2025).
Liang, W. C. et al. Structure- and machine learning-guided engineering reveal {that a} non-canonical disulfide in an anti-PD-1 rabbit antibody doesn’t impede antibody developability. MAbs 16, 2309685 (2024).
Wang, H., Hao, X., He, Y. & Fan, L. AbImmPred: an immunogenicity prediction methodology for therapeutic antibodies utilizing AntiBERTy-based sequence options. PLoS ONE 19, e0296737 (2024).
Bennett, N. R. et al. Atomically correct de novo design of single-domain antibodies with RFdiffusion. Preprint at bioRxiv (2025).
Chungyoun, M. & Gray, J. J. AI fashions for protein design are driving antibody engineering. Curr. Opin. Biomed. Eng. 28, 100473 (2023).
Zheng, J., Wang, Y., Liang, Q., Cui, L. & Wang, L. The software of machine studying on antibody discovery and optimization. Molecules 29, 5923 (2024).
Desnoyers, L. R. et al. Tumor-specific activation of an EGFR-targeting probody enhances therapeutic index. Sci. Transl. Med. 5, 207ra144 (2013).
Chang, H. W. et al. Generating tumor-selective conditionally energetic biologic anti-CTLA4 antibodies by way of protein-associated chemical switches. Proc. Natl Acad. Sci. USA 118, e2020606118 (2021).
Mimoto, F. et al. Exploitation of elevated extracellular ATP to particularly direct antibody to tumor microenvironment. Cell Rep. 33, 108542 (2020).
Kamata-Sakurai, M. et al. Antibody to CD137 activated by extracellular adenosine triphosphate Is tumor selective and broadly efficient in vivo with out systemic immune activation. Cancer Discov. 11, 158–175 (2021).
Hironiwa, N. et al. Calcium-dependent antigen binding as a novel modality for antibody recycling by endosomal antigen dissociation. MAbs 8, 65–73 (2016).
Chu, T. H., Patz, E. F. Jr. & Ackerman, M. E. Coming collectively on the hinges: therapeutic prospects of IgG3. MAbs 13, 1882028 (2021).
Keyt, B. A., Baliga, R., Sinclair, A. M., Carroll, S. F. & Peterson, M. S. Structure, operate, and therapeutic use of IgM antibodies. Antibodies 9, 53 (2020).
Buchner, J., Sitia, R. & Svilenov, H. L. Understanding IgM construction and biology to engineer new antibody therapeutics. BioDrugs 39, 347–357 (2025).
Bohländer, F. A brand new hope? Possibilities of therapeutic IgA antibodies within the therapy of inflammatory lung illnesses. Front. Immunol. 14, 1127339 (2023).
Candelaria, P. V., Nava, M., Daniels-Wells, T. R. & Penichet, M. L. A completely human IgE particular for CD38 as a possible remedy for a number of myeloma. Cancers 15, 4533 (2023).
Chauhan, J. et al. IgE antibodies in opposition to most cancers: efficacy and security. Antibodies 9, 55 (2020).
Ku, Z. et al. Nasal supply of an IgM presents broad safety from SARS-CoV-2 variants. Nature 595, 718–723 (2021).
Marks, L. The beginning pangs of monoclonal antibody therapeutics: the failure and legacy of Centoxin. MAbs 4, 403–412 (2012).
de Jong, R. N. et al. A novel platform for the potentiation of therapeutic antibodies based mostly on antigen-dependent formation of IgG hexamers on the cell floor. PLoS Biol. 14, e1002344 (2016). First demonstration of antigen-dependent IgG1 hexamerization (HexaBody know-how), which was enabling for a number of such antibodies which have reached medical trials.
Grandits, M. et al. Hybrid IgE-IgG1 antibodies (IgEG): a brand new antibody class that mixes IgE and IgG performance. MAbs 17, 2502673 (2025).
Carter, P. J. & Lazar, G. A. Next technology antibody medicine: pursuit of the ‘high-hanging fruit’. Nat. Rev. Drug Discov. 17, 197–223 (2018).
Lim, S. H., Beers, S. A., Al-Shamkhani, A. & Cragg, M. S. Agonist antibodies for most cancers immunotherapy: historical past, hopes, and challenges. Clin. Cancer Res. 30, 1712–1723 (2024).
Jhajj, H. S., Lwo, T. S., Yao, E. L. & Tessier, P. M. Unlocking the potential of agonist antibodies for treating most cancers utilizing antibody engineering. Trends Mol. Med. 29, 48–60 (2023).
Yen, M. et al. Facile discovery of surrogate cytokine agonists. Cell 185, 1414–1430.e1419 (2022).
Pekar, L., Krah, S. & Zielonka, S. Taming the beast: engineering methods and biomedical potential of antibody-based cytokine mimetics. Expert Opin. Biol. Ther. 24, 115–118 (2024).
Terstappen, G. C., Meyer, A. H., Bell, R. D. & Zhang, W. Strategies for delivering therapeutics throughout the blood–mind barrier. Nat. Rev. Drug Discov. 20, 362–383 (2021).
Yu, Y. J. et al. Boosting mind uptake of a therapeutic antibody by lowering its affinity for a transcytosis goal. Sci. Transl. Med. 3, 84ra44 (2011).
Grimm, H. P. et al. Delivery of the Brainshuttle amyloid-beta antibody fusion trontinemab to non-human primate mind and projected efficacious dose regimens in people. MAbs 15, 2261509 (2023).
Okuyama, T. et al. A section 2/3 trial of pabinafusp alfa, IDS fused with anti-human transferrin receptor antibody, concentrating on neurodegeneration in MPS-II. Mol. Ther. 29, 671–679 (2021). The fusion protein abinafusp alfa offers the primary medical proof of idea of utilizing transferrin-mediated transcytosis to boost supply of a protein therapeutic into the central nervous system.
Deng, B. et al. Oral nanomedicine: challenges and alternatives. Adv. Mater. 36, e2306081 (2024).
Nicze, M. et al. The present and promising oral supply strategies for protein- and peptide-based medicine. Int. J. Mol. Sci. 25, 815 (2024).
Abramson, A. et al. An ingestible self-orienting system for oral supply of macromolecules. Science 363, 611–615 (2019). Preclinical proof of idea of oral supply of a protein therapeutic (insulin) into systemic circulation utilizing a complicated ingestible medical machine.
Abramson, A. et al. Oral supply of systemic monoclonal antibodies, peptides and small molecules utilizing gastric auto-injectors. Nat. Biotechnol. 40, 103–109 (2022).
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).
Harris, C. T. & Cohen, S. Reducing immunogenicity by design: approaches to reduce immunogenicity of monoclonal antibodies. BioDrugs 38, 205–226 (2024).
Ridker, P. M. et al. Lipid-reduction variability and antidrug-antibody formation with bococizumab. N. Engl. J. Med. 376, 1517–1526 (2017).
Kearns, J. D. et al. A root trigger evaluation to establish the mechanistic drivers of immunogenicity in opposition to the anti-VEGF biotherapeutic brolucizumab. Sci. Transl. Med. 15, eabq5068 (2023).
Dyson, M. R. et al. Beyond affinity: choice of antibody variants with optimum biophysical properties and decreased immunogenicity from mammalian show libraries. MAbs 12, 1829335 (2020). Demonstration that bettering the biophysical properties of an antibody (bococizumab) correlates with decreased immunogenicity danger in nonclinical assays.
Schmitt, C. et al. Low immunogenicity of emicizumab in individuals with haemophilia A. Haemophilia 27, 984–992 (2021).
Sampei, Z. et al. Identification and multidimensional optimization of an uneven bispecific IgG antibody mimicking the operate of issue VIII cofactor exercise. PLoS ONE 8, e57479 (2013). Elegant antibody engineering that led to emicizumab, a bispecific antibody (to issue IXa and issue X) with a standard mild chain accredited for therapy of haemophilia A.
Ghosh, I., Gutka, H., Krause, M. E., Clemens, R. & Kashi, R. S. A scientific evaluate of economic excessive focus antibody drug merchandise accredited within the US: formulation composition, dosage type design and first packaging concerns. MAbs 15, 2205540 (2023).
Dall’Acqua, W. F. et al. Increasing the affinity of a human IgG1 for the neonatal Fc receptor: organic penalties. J. Immunol. 169, 5171–5180 (2002). Antibody engineering that led to the YTE (M252Y:S254T:T256E) triple Fc mutant, which has been used to increase the pharmacokinetic half-life of a number of accredited antibody therapeutics, together with nirsevimab, netakimab, amubarvimab and romlusevimab.
Gaudinski, M. R. et al. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: a section 1 open-label medical trial in wholesome adults. PLoS Med. 15, e1002493 (2018).
Robbie, G. J. et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an prolonged half-life in wholesome adults. Antimicrob. Agents Chemother. 57, 6147–6153 (2013). First demonstration of antibody half-life extension in human by utilizing Fc mutants (YTE, M252Y:S254T:T256E).
Zou, P. Predicting human bioavailability of subcutaneously administered fusion proteins and monoclonal antibodies utilizing human intravenous clearance or antibody isoelectric level. AAPS J. 25, 31 (2023).
Mulvey, A., Trueb, L., Coukos, G. & Arber, C. Novel methods to handle CAR-T cell toxicity. Nat. Rev. Drug Discov. 24, 379–397 (2025).
Oldham, R. Okay. Monoclonal antibodies in most cancers remedy. J. Clin. Oncol. 1, 582–590 (1983).
Ritz, J. & Schlossman, S. F. Utilization of monoclonal antibodies within the therapy of leukemia and lymphoma. Blood 59, 1–11 (1982).
Saleh, M. N. et al. A section II trial of murine monoclonal antibody 17-1A and interferon-γ: medical and immunological knowledge. Cancer Immunol. Immunother. 32, 185–190 (1990).
Shawler, D. L., Bartholomew, R. M., Smith, L. M. & Dillman, R. O. Human immune response to a number of injections of murine monoclonal IgG. J. Immunol. 135, 1530–1535 (1985).
Münz, M. et al. Side-by-side evaluation of 5 clinically examined anti-EpCAM monoclonal antibodies. Cancer Cell Int. 10, 44 (2010).
Goodman, G. E., Beaumier, P., Hellström, I., Fernyhough, B. & Hellström, Okay. E. Pilot trial of murine monoclonal antibodies in sufferers with superior melanoma. J. Clin. Oncol. 3, 340–352 (1985).
Vidarsson, G., Dekkers, G. & Rispens, T. IgG subclasses and allotypes: from construction to effector capabilities. Front. Immunol. 5, 520 (2014).
Ober, R. J., Radu, C. G., Ghetie, V. & Ward, E. S. Differences in promiscuity for antibody–FcRn interactions throughout species: implications for therapeutic antibodies. Int. Immunol. 13, 1551–1559 (2001).
Foote, J. & Winter, G. Antibody framework residues affecting the conformation of the hypervariable loops. J. Mol. Biol. 224, 487–499 (1992).
Rothe, C. et al. The human combinatorial antibody library HuCAL GOLD combines diversification of all six CDRs based on the pure immune system with a novel show methodology for environment friendly choice of high-affinity antibodies. J. Mol. Biol. 376, 1182–1200 (2008).
Hao, Y. et al. Synthetic integrin antibodies found by yeast show reveal alphaV subunit pairing preferences with beta subunits. MAbs 16, 2365891 (2024).
Porebski, B. T. et al. Rapid discovery of high-affinity antibodies by way of massively parallel sequencing, ribosome show and affinity screening. Nat. Biomed. Eng. 8, 214–232 (2024).
Lee, E. C. et al. Complete humanization of the mouse immunoglobulin loci allows environment friendly therapeutic antibody discovery. Nat. Biotechnol. 32, 356–363 (2014).
Murphy, A. J. et al. Mice with megabase humanization of their immunoglobulin genes generate antibodies as effectively as regular mice. Proc. Natl Acad. Sci. USA 111, 5153–5158 (2014).
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 area. J. Immunol. 190, 1481–1490 (2013).
Ouisse, L. H. et al. Antigen-specific single B cell sorting and expression-cloning from immunoglobulin humanized rats: a fast and versatile methodology for the technology of excessive affinity and discriminative human monoclonal antibodies. BMC Biotechnol. 17, 3 (2017).
Ros, F. et al. Rabbits transgenic for human IgG genes recapitulating rabbit B-cell biology to generate human antibodies of excessive specificity and affinity. MAbs 12, 1846900 (2020).
Ching, Okay. H. et al. Chickens with humanized immunoglobulin genes generate antibodies with excessive affinity and broad epitope protection to conserved targets. MAbs 10, 71–80 (2018).
Boyd, S. D. & Crowe, J. E. Jr. Deep sequencing and human antibody repertoire evaluation. Curr. Opin. Immunol. 40, 103–109 (2016).
Kelley, B. The historical past and potential way forward for monoclonal antibody therapeutics growth and manufacturing in 4 eras. MAbs 16, 2373330 (2024).
Carter, P. J. Introduction to present and future protein therapeutics: a protein engineering perspective. Exp. Cell. Res. 317, 1261–1269 (2011).
Hummel, J. et al. Modeling the downstream processing of monoclonal antibodies reveals price benefits for steady strategies for a broad vary of producing scales. Biotechnol. J. 14, e1700665 (2018).
Barnard, G. C., Zhou, M., Shen, A., Yuk, I. H. & Laird, M. W. Utilizing focused integration CHO swimming pools to probably speed up the GMP manufacturing of monoclonal and bispecific antibodies. Biotechnol. Prog. 40, e3399 (2024).
Glinšek, Okay., Bozovičar, Okay. & Bratkovič, T. CRISPR applied sciences in Chinese hamster ovary cell line engineering. Int. J. Mol. Sci. 24, 8144 (2023).
Ritacco, F. V., Wu, Y. & Khetan, A. Cell tradition media for recombinant protein expression in Chinese hamster ovary (CHO) cells: historical past, key elements, and optimization methods. Biotechnol. Prog. 34, 1407–1426 (2018).
Xu, W. J., Lin, Y., Mi, C. L., Pang, J. Y. & Wang, T. Y. Progress in fed-batch tradition for recombinant protein manufacturing in CHO cells. Appl. Microbiol. Biotechnol. 107, 1063–1075 (2023).
MacDonald, M. A. et al. Perfusion tradition of Chinese hamster ovary cells for bioprocessing purposes. Crit. Rev. Biotechnol. 42, 1099–1115 (2022).
Kumar, A., Udugama, I. A., Gargalo, C. L. & Gernaey, Okay. V. Why Is batch processing nonetheless dominating the biologics panorama? Towards an built-in steady bioprocessing various. Processes 8, 1641 (2020).
Dorival-García, N. et al. Large-scale evaluation of extractables and leachables in single-use luggage for biomanufacturing. Anal. Chem. 90, 9006–9015 (2018).
Amasawa, E., Kuroda, H., Okamura, Okay., Badr, S. & Sugiyama, H. Cost–profit evaluation of monoclonal antibody cultivation situations when it comes to life cycle environmental influence and working price. ACS Sustain. Chem. Eng. 9, 14012–14021 (2021).
Samaras, J. J., Micheletti, M. & Ding, W. Transformation of biopharmaceutical manufacturing by single-use applied sciences: present state, remaining challenges, and future growth. Annu. Rev. Chem. Biomol. Eng. 13, 73–97 (2022).
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