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Advances in antibody-based therapy in oncology

Nature Cancer volume 4, pages 165–180 (2023)Cite this article

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Abstract

Monoclonal antibodies are a growing class of targeted cancer therapeutics, characterized by exquisite specificity, long serum half-life, high affinity and immune effector functions. In this review, we outline key advances in the field with a particular focus on recent and emerging classes of engineered antibody therapeutic candidates, discuss molecular structure and mechanisms of action and provide updates on clinical development and practice.

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Fig. 1: Molecular engineering of monoclonal antibody therapeutics.
Fig. 2: Targets and mechanism of action of antibody-based therapeutics in oncology.
Fig. 3: Serum half-life of human IgG is prolonged by FcRn recycling.

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References

  1. Goulet, D. R. & Atkins, W. M. Considerations for the design of antibody-based therapeutics. J. Pharm. Sci. 109, 74–103 (2020).

    Article  CAS  PubMed  Google Scholar 

  2. Sliwkowski, M. X. & Mellman, I. Antibody therapeutics in cancer. Science 341, 1192–1198 (2013).

    Article  CAS  PubMed  Google Scholar 

  3. Pierpont, T. M., Limper, C. B. & Richards, K. L. Past, present, and future of rituximab—the world’s first oncology monoclonal antibody therapy. Front. Oncol. 8, 163 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Forecast, M.D. Global Cancer Monoclonal Antibodies Market Size, Share, Trends, COVID-19 Impact & Growth Analysis Report – Segmented By Application, Type, Conjugate Cancer Therapies & Region – Industry Forecast (2021 to 2026), Vol. 2021 (Market Data Forecast, 2021).

  5. Schroeder, H. W. Jr. & Cavacini, L. Structure and function of immunoglobulins. J. Allergy Clin. Immunol. 125, S41–S52 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  7. Akilesh, S. et al. Podocytes use FcRn to clear IgG from the glomerular basement membrane. Proc. Natl Acad. Sci. USA 105, 967–972 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Skowronek, M. H., Hendershot, L. M. & Haas, I. G. The variable domain of nonassembled Ig light chains determines both their half-life and binding to the chaperone BiP. Proc. Natl Acad. Sci. USA 95, 1574–1578 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mankarious, S. et al. The half-lives of IgG subclasses and specific antibodies in patients with primary immunodeficiency who are receiving intravenously administered immunoglobulin. J. Lab. Clin. Med. 112, 634–640 (1988).

    CAS  PubMed  Google Scholar 

  10. Ghetie, V. et al. Increasing the serum persistence of an IgG fragment by random mutagenesis. Nat. Biotechnol. 15, 637–640 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. Kim, J. K., Tsen, M. F., Ghetie, V. & Ward, E. S. Evidence that the hinge region plays a role in maintaining serum levels of the murine IgG1 molecule. Mol. Immunol. 32, 467–475 (1995).

    Article  CAS  PubMed  Google Scholar 

  12. Kontermann, R. E. Strategies for extended serum half-life of protein therapeutics. Curr. Opin. Biotechnol. 22, 868–876 (2011).

    Article  CAS  PubMed  Google Scholar 

  13. Liu, R., Oldham, R. J., Teal, E., Beers, S. A. & Cragg, M. S. Fc-engineering for modulated effector functions—improving antibodies for cancer treatment. Antibodies 9, 64 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Rouet, R. et al. Expression of high-affinity human antibody fragments in bacteria. Nat. Protoc. 7, 364 (2012).

    Article  CAS  PubMed  Google Scholar 

  15. Hwang, W. Y. & Foote, J. Immunogenicity of engineered antibodies. Methods 36, 3–10 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. 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).

    Article  CAS  PubMed  Google Scholar 

  17. Rouet, R., Lowe, D. & Christ, D. Stability engineering of the human antibody repertoire. FEBS Lett. 588, 269–277 (2014).

    Article  CAS  PubMed  Google Scholar 

  18. Dudgeon, K. et al. General strategy for the generation of human antibody variable domains with increased aggregation resistance. Proc. Natl Acad. Sci. USA 109, 10879–10884 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Weiner, G. J. Monoclonal antibody mechanisms of action in cancer. Immunol. Res. 39, 271–278 (2007).

    Article  CAS  PubMed  Google Scholar 

  20. Appert-Collin, A., Hubert, P., Crémel, G. & Bennasroune, A. Role of ErbB receptors in cancer cell migration and invasion. Front. Pharmacol. https://doi.org/10.3389/fphar.2015.00283 (2015).

  21. Fan, X. et al. VEGF blockade inhibits angiogenesis and reepithelialization of endometrium. FASEB J. 22, 3571–3580 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Glade-Bender, J., Kandel, J. J. & Yamashiro, D. J. VEGF blocking therapy in the treatment of cancer. Expert Opin. Biol. Ther. 3, 263–276 (2003).

    Article  CAS  PubMed  Google Scholar 

  23. Baselga, J. & Albanell, J. Mechanism of action of anti-HER2 monoclonal antibodies. Ann. Oncol. 12, S35–S41 (2001).

    Article  PubMed  Google Scholar 

  24. Meyer, S. et al. New insights in Type I and II CD20 antibody mechanisms of action with a panel of novel CD20 antibodies. Br. J. Haematol. 180, 808–820 (2018).

    Article  CAS  PubMed  Google Scholar 

  25. Chan, H. T. et al. CD20-induced lymphoma cell death is independent of both caspases and its redistribution into triton X-100 insoluble membrane rafts. Cancer Res. 63, 5480–5489 (2003).

    CAS  PubMed  Google Scholar 

  26. Honeychurch, J. et al. Antibody-induced nonapoptotic cell death in human lymphoma and leukemia cells is mediated through a novel reactive oxygen species-dependent pathway. Blood 119, 3523–3533 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ivanov, A. et al. Monoclonal antibodies directed to CD20 and HLA-DR can elicit homotypic adhesion followed by lysosome-mediated cell death in human lymphoma and leukemia cells. J. Clin. Invest. 119, 2143–2159 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Mone, A. P. et al. Alemtuzumab induces caspase-independent cell death in human chronic lymphocytic leukemia cells through a lipid raft-dependent mechanism. Leukemia 20, 272–279 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Tobinai, K., Klein, C., Oya, N. & Fingerle-Rowson, G. A review of obinutuzumab (GA101), a novel type II anti-CD20 monoclonal antibody, for the treatment of patients with B-cell malignancies. Adv. Ther. 34, 324–356 (2017).

    Article  CAS  PubMed  Google Scholar 

  30. Bologna, L. et al. Mechanism of action of type II, glycoengineered, anti-CD20 monoclonal antibody GA101 in B-chronic lymphocytic leukemia whole blood assays in comparison with rituximab and alemtuzumab. J. Immunol. 186, 3762–3769 (2011).

    Article  CAS  PubMed  Google Scholar 

  31. Snajdauf, M. et al. The TRAIL in the treatment of human cancer: an update on clinical trials. Front. Mol. Biosci. 8, 628332 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cardoso Alves, L., Corazza, N., Micheau, O. & Krebs, P. The multifaceted role of TRAIL signaling in cancer and immunity. FEBS J. 288, 5530–5554 (2021).

    Article  CAS  PubMed  Google Scholar 

  33. Wang, B. T. et al. Multimeric anti-DR5 IgM agonist antibody IgM-8444 is a potent inducer of cancer cell apoptosis and synergizes with chemotherapy and BCL-2 inhibitor ABT-199. Mol. Cancer Ther. 20, 2483–2494 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. van der Horst, H. J. et al. Potent preclinical activity of HexaBody-DR5/DR5 in relapsed and/or refractory multiple myeloma. Blood Adv. 5, 2165–2172 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Nimmerjahn, F., Gordan, S. & Lux, A. FcγR dependent mechanisms of cytotoxic, agonistic, and neutralizing antibody activities. Trends Immunol. 36, 325–336 (2015).

    Article  CAS  PubMed  Google Scholar 

  36. Clynes, R. A., Towers, T. L., Presta, L. G. & Ravetch, J. V. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat. Med. 6, 443–446 (2000).

    Article  CAS  PubMed  Google Scholar 

  37. Nimmerjahn, F. & Ravetch, J. V. Divergent immunoglobulin G subclass activity through selective Fc receptor binding. Science 310, 1510–1512 (2005).

    Article  CAS  PubMed  Google Scholar 

  38. Stewart, R., Hammond, S.A., Oberst, M. & Wilkinson, R.W. The role of Fc γ receptors in the activity of immunomodulatory antibodies for cancer. J. ImmunoTher. Cancer https://doi.org/10.1186/s40425-014-0029-x (2014).

  39. Brüggemann, M. et al. Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J. Exp. Med. 166, 1351–1361 (1987).

    Article  PubMed  Google Scholar 

  40. Kaneko, Y., Nimmerjahn, F., & Ravetch, J . V. Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313, 670–673 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. de Taeye, S. W. et al. FcγR binding and ADCC activity of human IgG allotypes. Front. Immunol. 11, 740 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Lu, L. L., Suscovich, T. J., Fortune, S. M. & Alter, G. Beyond binding: antibody effector functions in infectious diseases. Nat. Rev. Immunol. 18, 46–61 (2018).

    Article  CAS  PubMed  Google Scholar 

  43. Musolino, A. et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J. Clin. Oncol. 26, 1789–1796 (2008).

    Article  CAS  PubMed  Google Scholar 

  44. 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).

    Article  CAS  PubMed  Google Scholar 

  45. Kennedy, A. D. et al. Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia. J. Immunol. 172, 3280–3288 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Vanderven, H. A., Jegaskanda, S., Wheatley, A. K. & Kent, S. J. Antibody-dependent cellular cytotoxicity and influenza virus. Curr. Opin. Virol. 22, 89–96 (2017).

    Article  CAS  PubMed  Google Scholar 

  47. Pereira, N. A., Chan, K. F., Lin, P. C. & Song, Z. The ‘less-is-more’ in therapeutic antibodies: afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity. mAbs 10, 693–711 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wang, W., Erbe, A. K., Hank, J. A., Morris, Z. S. & Sondel, P. M. NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy. Front. Immunol. 6, 368 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Uchida, J. et al. The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy. J. Exp. Med. 199, 1659–1669 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lehmann, B. et al. Tumor location determines tissue-specific recruitment of tumor-associated macrophages and antibody-dependent immunotherapy response. Sci. Immunol. 2, eaah6413 (2017).

    Article  PubMed  Google Scholar 

  51. Gül, N. & van Egmond, M. Antibody-dependent phagocytosis of tumor cells by macrophages: a potent effector mechanism of monoclonal antibody therapy of cancer. Cancer Res. 75, 5008–5013 (2015).

    Article  PubMed  Google Scholar 

  52. Herbst, C. et al. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin’s lymphoma: a systematic review. Haematologica 95, 494–500 (2010).

    Article  CAS  PubMed  Google Scholar 

  53. Beers, S. A. et al. Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection. Blood 115, 5191–5201 (2010).

    Article  CAS  PubMed  Google Scholar 

  54. Albanesi, M. et al. Neutrophils mediate antibody-induced antitumor effects in mice. Blood 122, 3160–3164 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Siders, W. M. et al. Involvement of neutrophils and natural killer cells in the anti-tumor activity of alemtuzumab in xenograft tumor models. Leuk. Lymphoma 51, 1293–1304 (2010).

    Article  CAS  PubMed  Google Scholar 

  56. Zhu, E. F. et al. Synergistic innate and adaptive immune response to combination immunotherapy with anti-tumor antigen antibodies and extended serum half-life IL-2. Cancer Cell 27, 489–501 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Matlung, H. L. et al. Neutrophils kill antibody-opsonized cancer cells by trogoptosis. Cell Rep. 23, 3946–3959 (2018).

    Article  CAS  PubMed  Google Scholar 

  58. Ring, N. G. et al. Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage antitumor activity. Proc. Natl Acad. Sci. USA 114, E10578–E10585 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Vitale, M., Cantoni, C., Pietra, G., Mingari, M. C. & Moretta, L. Effect of tumor cells and tumor microenvironment on NK cell function. Eur. J. Immunol. 44, 1582–1592 (2014).

    Article  CAS  PubMed  Google Scholar 

  60. Melero, I., Rouzaut, A., Motz, G. T. & Coukos, G. T-cell and NK-cell infiltration into solid tumors: a key limiting factor for efficacious cancer immunotherapy. Cancer Discov. 4, 522–526 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Herter, S. et al. Glycoengineering of therapeutic antibodies enhances monocyte/macrophage-mediated phagocytosis and cytotoxicity. J. Immunol. 192, 2252–2260 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gigon, L., Yousefi, S., Karaulov, A. & Simon, H. U. Mechanisms of toxicity mediated by neutrophil and eosinophil granule proteins. Allergol. Int. 70, 30–38 (2021).

    Article  CAS  PubMed  Google Scholar 

  63. Valgardsdottir, R. et al. Human neutrophils mediate trogocytosis rather than phagocytosis of CLL B cells opsonized with anti-CD20 antibodies. Blood 129, 2636–2644 (2017).

    Article  CAS  PubMed  Google Scholar 

  64. Velmurugan, R., Challa, D. K., Ram, S., Ober, R. J. & Ward, E. S. Macrophage-mediated trogocytosis leads to death of antibody-opsonized tumor cells. Mol. Cancer Ther. 15, 1879–1889 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Taylor, R. P. & Lindorfer, M. A. Fcγ-receptor-mediated trogocytosis impacts mAb-based therapies: historical precedence and recent developments. Blood 125, 762–766 (2015).

    Article  CAS  PubMed  Google Scholar 

  66. Vazquez-Lombardi, R., Nevoltris, D., Rouet, R. & Christ, D. Expression of IgG monoclonals with engineered immune effector functions. Methods Mol. Biol. 1827, 313–334 (2018).

    Article  CAS  PubMed  Google Scholar 

  67. Golay, J. & Taylor, R. P. The role of complement in the mechanism of action of therapeutic anti-cancer mAbs. Antibodies 9, 58 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Cragg, M. S. et al. Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts. Blood 101, 1045–1052 (2003).

    Article  CAS  PubMed  Google Scholar 

  69. Marshall, M. J. E., Stopforth, R. J. & Cragg, M. S. Therapeutic antibodies: what have we learnt from targeting CD20 and where are we going? Front. Immunol. 8, 1245 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Waldman, A. D., Fritz, J. M. & Lenardo, M. J. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat. Rev. Immunol. 20, 651–668 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Brunet, J.-F. et al. A new member of the immunoglobulin superfamily—CTLA-4. Nature 328, 267–270 (1987).

    Article  CAS  PubMed  Google Scholar 

  72. Krummel, M. F. & Allison, J. P. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J. Exp. Med. 182, 459–465 (1995).

    Article  CAS  PubMed  Google Scholar 

  73. Linsley, P. S. et al. CTLA-4 is a second receptor for the B cell activation antigen B7. J. Exp. Med. 174, 561–569 (1991).

    Article  CAS  PubMed  Google Scholar 

  74. Seidel, J. A., Otsuka, A. & Kabashima, K. Anti-PD-1 and anti-CTLA-4 therapies in cancer: mechanisms of action, efficacy, and limitations. Front. Oncol. 8, 86 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Twomey, J. D. & Zhang, B. Cancer immunotherapy update: FDA-approved checkpoint inhibitors and companion diagnostics. AAPS J. 23, 39 (2021).

    Article  PubMed  Google Scholar 

  76. Haymaker, C., Wu, R., Bernatchez, C. & Radvanyi, L. PD-1 and BTLA and CD8(+) T-cell ‘exhaustion’ in cancer: ‘exercising’ an alternative viewpoint. Oncoimmunology 1, 735–738 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Lee, J., Ahn, E., Kissick, H. T. & Ahmed, R. Reinvigorating exhausted T cells by blockade of the PD-1 pathway. For. Immunopathol. Dis. Therap. 6, 7–17 (2015).

    PubMed  PubMed Central  Google Scholar 

  78. Pardoll, D. M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12, 252–264 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

    Article  CAS  PubMed  Google Scholar 

  80. Akinleye, A. & Rasool, Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J. Hematol. Oncol. https://doi.org/10.1186/s13045-019-0779-5 (2019).

  81. Qin, S. et al. Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4. Mol. Cancer 18, 155 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Huang, R. Y. et al. LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model. Oncotarget 6, 27359–27377 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Johnston, R. J. et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function. Cancer Cell 26, 923–937 (2014).

    Article  CAS  PubMed  Google Scholar 

  84. Sakuishi, K. et al. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J. Exp. Med. 207, 2187–2194 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Long, G. V. et al. Relatlimab and nivolumab versus nivolumab in previously untreated metastatic or unresectable melanoma: overall survival and response rates from RELATIVITY-047 (CA224-047). J. Clin. Oncol. 40, 360385–360385 (2022).

    Article  Google Scholar 

  86. Rudin, C. M. et al. Rudin, C.M. et al. SKYSCRAPER-02: primary results of a phase III, randomized, double-blind, placebo-controlled study of atezolizumab (atezo) + carboplatin + etoposide (CE) with or without tiragolumab (tira) in patients (pts) with untreated extensive-stage small cell lung cancer (ES-SCLC). J. Clin. Oncol. 40, LBA8507 (2022).

    Article  Google Scholar 

  87. Garber, K. Immune agonist antibodies face critical test. Nat. Rev. Drug Discov. 19, 3–5 (2020).

    Article  CAS  PubMed  Google Scholar 

  88. Shi, S. Y. et al. A biparatopic agonistic antibody that mimics fibroblast growth factor 21 ligand activity. J. Biol. Chem. 293, 5909–5919 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Qi, X. et al. Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcγR affinity. Nat. Commun. 10, 2141 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Suntharalingam, G. et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N. Engl. J. Med. 355, 1018–1028 (2006).

    Article  CAS  PubMed  Google Scholar 

  91. Segal, N. H. et al. Results from an integrated safety analysis of urelumab, an agonist anti-CD137 monoclonal antibody. Clin. Cancer Res. 23, 1929–1936 (2017).

    Article  CAS  PubMed  Google Scholar 

  92. Segal, N. H. et al. Phase I study of single-agent utomilumab (PF-05082566), a 4-1BB/CD137 agonist, in patients with advanced cancer. Clin. Cancer Res. 24, 1816–1823 (2018).

    Article  CAS  PubMed  Google Scholar 

  93. Wilson, N. S. et al. An Fcγ receptor-dependent mechanism drives antibody-mediated target-receptor signaling in cancer cells. Cancer Cell 19, 101–113 (2011).

    Article  CAS  PubMed  Google Scholar 

  94. Bulliard, Y. et al. OX40 engagement depletes intratumoral Tregs via activating FcγRs, leading to antitumor efficacy. Immunol. Cell Biol. 92, 475–480 (2014).

    Article  CAS  PubMed  Google Scholar 

  95. Coe, D. et al. Depletion of regulatory T cells by anti-GITR mAb as a novel mechanism for cancer immunotherapy. Cancer Immunol. Immunother. 59, 1367–1377 (2010).

    Article  CAS  PubMed  Google Scholar 

  96. Simpson, T. R. et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J. Exp. Med. 210, 1695–1710 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Bulliard, Y. et al. Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. J. Exp. Med. 210, 1685–1693 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Chau, I. et al. Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): first results of the CheckMate 648 study. J. Clin. Oncol. 39, LBA4001–LBA4001 (2021).

    Article  Google Scholar 

  99. Vazquez-Lombardi, R. et al. Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells. Nat. Commun. 8, 1–12 (2017).

    Article  Google Scholar 

  100. Ehrlich, P. Die Aufgaben der Chemotherapie. Frankfurter Zeitung und Handelsblatt (4 September 1906).

  101. Chari, R. V. J., Miller, M. L. & Widdison, W. C. Antibody–drug conjugates: an emerging concept in cancer therapy. Angew. Chem. Int. Ed. 53, 3796–3827 (2014).

    Article  CAS  Google Scholar 

  102. Mullard, A. Maturing antibody–drug conjugate pipeline hits 30. Nat. Rev. Drug Discov. 12, 329–332 (2013).

    Article  CAS  PubMed  Google Scholar 

  103. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Shitara, K. et al. Discovery and development of trastuzumab deruxtecan and safety management for patients with HER2-positive gastric cancer. Gastric Cancer 24, 780–789 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Chau, C. H., Steeg, P. S. & Figg, W. D. Antibody–drug conjugates for cancer. Lancet 394, 793–804 (2019).

    Article  CAS  PubMed  Google Scholar 

  106. Lassiter, G. et al. Belantamab mafodotin to treat multiple myeloma: a comprehensive review of disease, drug efficacy and side effects. Curr. Oncol. 28, 640–660 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Lamb, Y. N. Inotuzumab ozogamicin: first global approval. Drugs 77, 1603–1610 (2017).

    Article  CAS  PubMed  Google Scholar 

  108. Geman, D., d’Avignon, C., Naiman, D. Q. & Winslow, R. L. Classifying gene expression profiles from pairwise mRNA comparisons. Stat. Appl. Genet. Mol.Biol. 3, 19 (2004).

    Article  Google Scholar 

  109. Razzaghdoust, A. et al. Data-driven discovery of molecular targets for antibody–drug conjugates in cancer treatment. BioMed. Res. Int. 2021, 2670573 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Dott, J., Abila, B. & Wuerthner, J. U. Current trends in the clinical development of antibody–drug conjugates in oncology. Pharmaceut. Med. 32, 259–273 (2018).

    CAS  Google Scholar 

  111. Hartley, J. A. et al. Pre-clinical pharmacology and mechanism of action of SG3199, the pyrrolobenzodiazepine (PBD) dimer warhead component of antibody-drug conjugate (ADC) payload tesirine. Sci. Rep. 8, 10479 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Damle, N. K. & Frost, P. Antibody-targeted chemotherapy with immunoconjugates of calicheamicin. Curr. Opin. Pharmacol. 3, 386–390 (2003).

    Article  CAS  PubMed  Google Scholar 

  113. Lee, A. Loncastuximab tesirine: first approval. Drugs 81, 1229–1233 (2021).

    Article  CAS  PubMed  Google Scholar 

  114. Jen, E. Y. et al. FDA approval: gemtuzumab ozogamicin for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia. Clin. Cancer Res. 24, 3242–3246 (2018).

    Article  CAS  PubMed  Google Scholar 

  115. Rossi, C., Chrétien, M. L. & Casasnovas, R. O. Antibody–drug conjugates for the treatment of hematological malignancies: a comprehensive review. Target Oncol. 13, 287–308 (2018).

    Article  PubMed  Google Scholar 

  116. Chen, H. et al. Synthesis and antitumor activity of novel arylpiperazine derivatives containing the saccharin moiety. Molecules 22, 1857 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  117. Ballantyne, A. & Dhillon, S. Trastuzumab emtansine: first global approval. Drugs 73, 755–765 (2013).

    Article  CAS  PubMed  Google Scholar 

  118. Chang, E. et al. FDA approval summary: enfortumab vedotin for locally advanced or metastatic urothelial carcinoma. Clin. Cancer Res. 27, 922–927 (2021).

    Article  CAS  PubMed  Google Scholar 

  119. Deeks, E. D. Polatuzumab vedotin: first global approval. Drugs 79, 1467–1475 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Perez, J. et al. Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond. Expert Opin. Biol. Ther. 21, 811–824 (2021).

    Article  CAS  PubMed  Google Scholar 

  121. Wahby, S. et al. FDA approval summary: accelerated approval of sacituzumab govitecan-hziy for third-line treatment of metastatic triple-negative breast cancer. Clin. Cancer Res. 27, 1850–1854 (2021).

    Article  CAS  PubMed  Google Scholar 

  122. Thomas, A. & Pommier, Y. Targeting topoisomerase I in the era of precision medicine. Clin. Cancer Res. 25, 6581–6589 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Tsuchikama, K. & An, Z. Antibody–drug conjugates: recent advances in conjugation and linker chemistries. Protein Cell 9, 33–46 (2018).

    Article  CAS  PubMed  Google Scholar 

  124. Beck, A., Goetsch, L., Dumontet, C. & Corvaïa, N. Strategies and challenges for the next generation of antibody–drug conjugates. Nat. Rev. Drug Discov. 16, 315–337 (2017).

    Article  CAS  PubMed  Google Scholar 

  125. Bargh, J. D., Isidro-Llobet, A., Parker, J. S. & Spring, D. R. Cleavable linkers in antibody–drug conjugates. Chem. Soc. Rev. 48, 4361–4374 (2019).

    Article  CAS  PubMed  Google Scholar 

  126. Kovtun, Y. V. et al. Antibody–drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen. Cancer Res. 66, 3214–3221 (2006).

    Article  CAS  PubMed  Google Scholar 

  127. Staudacher, A. H. & Brown, M. P. Antibody–drug conjugates and bystander killing: is antigen-dependent internalisation required? Br. J. Cancer 117, 1736–1742 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Walles, M., Connor, A. & Hainzl, D. ADME and safety aspects of non-cleavable linkers in drug discovery and development. Curr. Top. Med. Chem. 17, 3463–3475 (2017).

    Article  CAS  PubMed  Google Scholar 

  129. 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).

    Article  CAS  PubMed  Google Scholar 

  130. Erickson, H. K. et al. Antibody–maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res. 66, 4426–4433 (2006).

    Article  CAS  PubMed  Google Scholar 

  131. Loganzo, X. T. Antibody–drug conjugate payloads induce markers of immunogenic cell death in cancer cells. Cancer Res. 78, 2757 (2018).

    Article  Google Scholar 

  132. Müller, P. et al. Microtubule-depolymerizing agents used in antibody–drug conjugates induce antitumor immunity by stimulation of dendritic cells. Cancer Immunol. Res. 2, 741–755 (2014).

    Article  PubMed  Google Scholar 

  133. Müller, P. et al. Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade. Sci. Transl. Med. 7, 315ra188 (2015).

    Article  PubMed  Google Scholar 

  134. Rios-Doria, J. et al. Antibody–drug conjugates bearing pyrrolobenzodiazepine or tubulysin payloads are immunomodulatory and synergize with multiple immunotherapies. Cancer Res. 77, 2686–2698 (2017).

    Article  CAS  PubMed  Google Scholar 

  135. Iwata, T. N. et al. A HER2-targeting antibody-drug conjugate, trastuzumab deruxtecan (DS-8201a), enhances antitumor immunity in a mouse model. Mol. Cancer Ther. 17, 1494–1503 (2018).

    Article  CAS  PubMed  Google Scholar 

  136. Galluzzi, L., Buqué, A., Kepp, O., Zitvogel, L. & Kroemer, G. Immunogenic cell death in cancer and infectious disease. Nat. Rev. Immunol. 17, 97–111 (2017).

    Article  CAS  PubMed  Google Scholar 

  137. Rosenberg, J. E. et al. Study EV-103: preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. J. Clin. Oncol. https://doi.org/10.1200/JCO.2020.38.6_suppl.441 (2020).

  138. Schmid, P. et al. BEGONIA: phase 1b/2 study of durvalumab (D) combinations in locally advanced/metastatic triple-negative breast cancer (TNBC)—initial results from arm 1, d+paclitaxel (P), and arm 6, d+trastuzumab deruxtecan (T-DXd). J. Clin. Oncol. https://doi.org/10.1200/JCO.2021.39.15_suppl.1023 (2021).

  139. Leppek, K., Das, R. & Barna, M. Functional 5′ UTR mRNA structures in eukaryotic translation regulation and how to find them. Nat. Rev. Mol. Cell Biol. 19, 158–174 (2018).

    Article  CAS  PubMed  Google Scholar 

  140. Indini, A., Rijavec, E. & Grossi, F. Trastuzumab deruxtecan: changing the destiny of HER2 expressing solid tumors. Int. J. Mol. Sci. 22, 4774 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Bardia, A. et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N. Engl. J. Med. 384, 1529–1541 (2021).

    Article  CAS  PubMed  Google Scholar 

  142. Li, Z. et al. Influence of molecular size on tissue distribution of antibody fragments. MAbs 8, 113–119 (2016).

    Article  CAS  PubMed  Google Scholar 

  143. Vazquez-Lombardi, R. et al. Challenges and opportunities for non-antibody scaffold drugs. Drug Discov. Today 20, 1271–1283 (2015).

    Article  CAS  PubMed  Google Scholar 

  144. Zhou, S., Liu, M., Ren, F., Meng, X. & Yu, J. The landscape of bispecific T cell engager in cancer treatment. Biomarker Res. 9, 38 (2021).

    Article  Google Scholar 

  145. Nagorsen, D., Kufer, P., Baeuerle, P. A. & Bargou, R. Blinatumomab: a historical perspective. Pharmacol. Ther. 136, 334–342 (2012).

    Article  CAS  PubMed  Google Scholar 

  146. Ojemolon, P. E., Kalidindi, S., Ahlborn, T. A., Aihie, O. P. & Awoyomi, M. I. Cytokine release syndrome following blinatumomab therapy. Cureus 14, e21583 (2022).

    PubMed  PubMed Central  Google Scholar 

  147. Przepiorka, D. et al. FDA approval: blinatumomab. Clin. Cancer Res. 21, 4035–4039 (2015).

    Article  CAS  PubMed  Google Scholar 

  148. Tian, Z., Liu, M., Zhang, Y. & Wang, X. Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies. J. Hematol. Oncol. 14, 75 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Wei, A. H. et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood 135, 2137–2145 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Hutchings, M. et al. Glofitamab, a novel, bivalent CD20-targeting T-cell-engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: a phase I trial. J. Clin. Oncol. 39, 1959–1970 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Dickinson, M. et al. Glofitamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and ≥ 2 prior therapies: pivotal phase II expansion results. J. Clin. Oncol. 40, 7500 (2022).

    Article  Google Scholar 

  152. Einsele, H. et al. The BiTE (bispecific T-cell engager) platform: development and future potential of a targeted immuno-oncology therapy across tumor types. Cancer 126, 3192–3201 (2020).

    Article  CAS  PubMed  Google Scholar 

  153. Subklewe, M. BiTEs better than CAR T cells. Blood Adv. 5, 607–612 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Jones, H. F., Molvi, Z., Klatt, M. G., Dao, T. & Scheinberg, D. A. Empirical and rational design of T cell receptor-based immunotherapies. Front. Immunol. 11, 585385 (2020).

    Article  CAS  PubMed  Google Scholar 

  155. Chang, A. Y. et al. Opportunities and challenges for TCR mimic antibodies in cancer therapy. Expert Opin. Biol. Ther. 16, 979–987 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Nathan, P. et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N. Engl. J. Med. 385, 1196–1206 (2021).

    Article  CAS  PubMed  Google Scholar 

  157. Sgouros, G., Bodei, L., McDevitt, M. R. & Nedrow, J. R. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat. Rev. Drug Discov. 19, 589–608 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Marcu, L., Bezak, E. & Allen, B. J. Global comparison of targeted α vs targeted β therapy for cancer: In vitro, in vivo and clinical trials. Crit. Rev. Oncol. Hematol. 123, 7–20 (2018).

    Article  PubMed  Google Scholar 

  159. Morris, M. J. et al. Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). J. Clin. Oncol. 39, LBA4 (2021).

    Article  Google Scholar 

  160. Shields, R. L. et al. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcγ RIII and antibody-dependent cellular toxicity. J. Biol. Chem. 277, 26733–26740 (2002).

    Article  CAS  PubMed  Google Scholar 

  161. Narimatsu, Y. et al. Genetic glycoengineering in mammalian cells. J. Biol. Chem. 296, 100448 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Stapleton, N. M. et al. Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential. Nat. Commun. 2, 599 (2011).

    Article  PubMed  Google Scholar 

  163. Lu, Q., Huang, H., Tang, S., Wang, Y. & Yang, D. H. Tafasitamab for refractory/relapsed diffuse large B-cell lymphoma. Drugs Today 57, 571–580 (2021).

    Article  CAS  Google Scholar 

  164. Tarantino, P. et al. Margetuximab for the treatment of HER2-positive metastatic breast cancer. Expert Opin. Biol. Ther. 21, 127–133 (2021).

    Article  CAS  PubMed  Google Scholar 

  165. Roopenian, D. C. & Akilesh, S. FcRn: the neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7, 715–725 (2007).

    Article  CAS  PubMed  Google Scholar 

  166. Beers, S. A., Glennie, M. J. & White, A. L. Influence of immunoglobulin isotype on therapeutic antibody function. Blood 127, 1097–1101 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. White, A. L. et al. Interaction with FcγRIIB is critical for the agonistic activity of anti-CD40 monoclonal antibody. J. Immunol. 187, 1754–1763 (2011).

    Article  CAS  PubMed  Google Scholar 

  168. White, A. L., Beers, S. A. & Cragg, M. S. FcγRIIB as a key determinant of agonistic antibody efficacy. Curr. Top. Microbiol. Immunol. 382, 355–372 (2014).

    CAS  PubMed  Google Scholar 

  169. Roschewski, M. & Hill, B. T. One size does not fit all: who benefits from maintenance after frontline therapy for follicular lymphoma? Am. Soc. Clin. Oncol. Educ. Book 39, 467–476 (2019).

    Article  PubMed  Google Scholar 

  170. Centanni, M., Moes, D. J. A. R., Trocóniz, I. F., Ciccolini, J. & van Hasselt, J. G. C. Clinical pharmacokinetics and pharmacodynamics of immune checkpoint inhibitors. Clin. Pharmacokinet. 58, 835–857 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  171. Ugurlar, D. et al. Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement. Science 359, 794–797 (2018).

    Article  CAS  PubMed  Google Scholar 

  172. Moore, G. L., Chen, H., Karki, S. & Lazar, G. A. Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. mAbs 2, 181–189 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Diebolder, C. A. et al. Complement is activated by IgG hexamers assembled at the cell surface. Science 343, 1260–1263 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Lazar, G. A. et al. Engineered antibody Fc variants with enhanced effector function. Proc. Natl Acad. Sci. USA 103, 4005–4010 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Ibrahim, R., Stewart, R. & Shalabi, A. PD-L1 blockade for cancer treatment: MEDI4736. Semin. Oncol. 42, 474–483 (2015).

    Article  CAS  PubMed  Google Scholar 

  176. Inman, B. A., Longo, T. A., Ramalingam, S. & Harrison, M. R. Atezolizumab: a PD-L1-blocking antibody for bladder cancer. Clin. Cancer Res. 23, 1886–1890 (2017).

    Article  CAS  PubMed  Google Scholar 

  177. Liu, S.-Y. & Wu, Y.-L. Tislelizumab: an investigational anti-PD-1 antibody for the treatment of advanced non-small cell lung cancer (NSCLC). Expert Opin. Investig. Drugs 29, 1355–1364 (2020).

    Article  CAS  PubMed  Google Scholar 

  178. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Pellizzari, G. et al. Harnessing therapeutic IgE antibodies to re-educate macrophages against cancer. Trends Mol. Med. 26, 615–626 (2020).

    Article  CAS  PubMed  Google Scholar 

  180. Bruhns, P. & Jönsson, F. Mouse and human FcR effector functions. Immunol. Rev. 268, 25–51 (2015).

    Article  CAS  PubMed  Google Scholar 

  181. Brinkhaus, M. et al. Human IgE does not bind to human FcRn. Sci. Rep. 12, 62 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Blumberg, L. J. et al. Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses. Sci. Adv. 5, eaax9586 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Vieira, P. & Rajewsky, K. The half-lives of serum immunoglobulins in adult mice. Eur. J. Immunol. 18, 313–316 (1988).

    Article  CAS  PubMed  Google Scholar 

  184. Neri, D. Antibody–cytokine fusions: versatile products for the modulation of anticancer immunity. Cancer Immunol. Res. 7, 348–354 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Bonati, L. & Tang, L. Cytokine engineering for targeted cancer immunotherapy. Curr. Opin. Chem. Biol. 62, 43–52 (2021).

    Article  CAS  PubMed  Google Scholar 

  186. Holder, P. G. et al. Engineering interferons and interleukins for cancer immunotherapy. Adv. Drug Deliv. Rev. 182, 114112 (2022).

    Article  CAS  PubMed  Google Scholar 

  187. Young, P. A., Morrison, S. L. & Timmerman, J. M. Antibody–cytokine fusion proteins for treatment of cancer: engineering cytokines for improved efficacy and safety. Semin. Oncol. 41, 623–636 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Overwijk, W. W., Tagliaferri, M. A. & Zalevsky, J. Engineering IL-2 to give new life to T cell immunotherapy. Annu. Rev. Med. 72, 281–311 (2021).

    Article  CAS  PubMed  Google Scholar 

  189. Waldhauer, I. et al. Simlukafusp alfa (FAP-IL2v) immunocytokine is a versatile combination partner for cancer immunotherapy. MAbs 13, 1913791 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  190. Ratcliff, M., Zhou, R. X., Jermutus, L. & Hyvönen, M. The role of pro-domains in human growth factors and cytokines. Biochem. Soc. Trans. 49, 1963–1973 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Elter, A. et al. Protease-activation of Fc-masked therapeutic antibodies to alleviate off-tumor cytotoxicity. Front. Immunol. 12, 715719 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Beck, A., Wurch, T., Bailly, C. & Corvaia, N. Strategies and challenges for the next generation of therapeutic antibodies. Nat. Rev. Immunol. 10, 345–352 (2010).

    Article  CAS  PubMed  Google Scholar 

  193. Liu, H. et al. In vitro and in vivo modifications of recombinant and human IgG antibodies. MAbs 6, 1145–1154 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Lee, C. H. et al. IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions. Nat. Immunol. 18, 889–898 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Montoyo, H. P. et al. Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice. Proc. Natl Acad. Sci. USA 106, 2788–2793 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Pyzik, M., Rath, T., Lencer, W. I., Baker, K. & Blumberg, R. S. FcRn: the architect behind the immune and nonimmune functions of IgG and albumin. J. Immunol. 194, 4595–4603 (2015).

    Article  CAS  PubMed  Google Scholar 

  197. Ward, E. S. et al. From sorting endosomes to exocytosis: association of Rab4 and Rab11 GTPases with the Fc receptor, FcRn, during recycling. Mol. Biol. Cell 16, 2028–2038 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Kim, J. K. et al. Mapping the site on human IgG for binding of the MHC class I-related receptor, FcRn. Eur. J. Immunol. 29, 2819–2825 (1999).

    Article  CAS  PubMed  Google Scholar 

  199. Kontermann, R. E. Strategies to extend plasma half-lives of recombinant antibodies. BioDrugs 23, 93–109 (2009).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

S.Z., R.V.L. and D.C. wrote the manuscript with input from all authors. R.V.L. generated the figures. D.C. acknowledges funding from the National Health and Medical Research Council (1157744).

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  1. Rodrigo Vazquez-Lombardi

    Present address: Engimmune Therapeutics, Allschwil, Switzerland

Authors and Affiliations

  1. Garvan Institute of Medical Research, Sydney, New South Wales, Australia

    Sacha Zinn, Rodrigo Vazquez-Lombardi & Daniel Christ

  2. Faculty of Medicine, The University of New South Wales, St Vincent’s Clinical School, Darlinghurst, Sydney, New South Wales, Australia

    Sacha Zinn, Rodrigo Vazquez-Lombardi & Daniel Christ

  3. University of San Diego, Knauss School of Business, San Diego, CA, USA

    Carsten Zimmermann

  4. University of California San Diego, La Jolla, CA, USA

    Carsten Zimmermann

  5. AstraZeneca, Oncology R&D, Biologics Engineering & Targeted Delivery, Gaithersburg, MD, USA

    Puja Sapra

  6. AstraZeneca, BioPharmaceuticals R&D, Research & Early Development, Cambridge, UK

    Lutz Jermutus

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Zinn, S., Vazquez-Lombardi, R., Zimmermann, C. et al. Advances in antibody-based therapy in oncology. Nat Cancer 4, 165–180 (2023). https://doi.org/10.1038/s43018-023-00516-z

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