A pivotal decade for bispecific antibodies?

References

• Labrijn AF, Janmaat ML, Reichert JM, Parren P. Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019;18(8):585–9. doi:10.1038/s41573-019-0028-1. PMID: 31175342.
   PubMed Web of Science ®Google Scholar
• Brinkmann U, Kontermann RE. The making of bispecific antibodies. MAbs. 2017;9(2):182–212. doi:10.1080/19420862.2016.1268307. PMID: 28071970.
   PubMed Web of Science ®Google Scholar
• Brinkmann U, Kontermann RE. Bispecific antibodies. Science. 2021;372(6545):916–17. doi:10.1126/science.abg1209. PMID: 34045345.
   PubMed Web of Science ®Google Scholar
• Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today. 2015;20(7):838–47. doi:10.1016/j.drudis.2015.02.008. PMID: 25728220.
   PubMed Web of Science ®Google Scholar
• Klein C, Brinkmann U, Reichert JM, Kontermann RE. The present and future of bispecific antibodies for cancer therapy. Nat Rev Drug Discov. 2024. in press. doi:10.1038/s41573-024-00896-6.
   PubMed Web of Science ®Google Scholar
• Seimetz D, Lindhofer H, Bokemeyer C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM×anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010;36(6):458–67. doi:10.1016/j.ctrv.2010.03.001. PMID: 20347527.
   PubMed Web of Science ®Google Scholar
• Sanford M. Blinatumomab: first global approval. Drugs. 2015;75(3):321–27. doi:10.1007/s40265-015-0356-3. PMID: 25637301.
   PubMed Web of Science ®Google Scholar
• Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, Noppeney R, Viardot A, Hess G, Schuler M. et al. Tumor regression in cancer patients by very low doses of a T cell–engaging antibody. Science. 2008;321(5891):974–77. doi:10.1126/science.1158545. PMID: 18703743.
   PubMed Web of Science ®Google Scholar
• Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R. et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–47. doi:10.1056/NEJMoa1609783. PMID: 28249141.
   PubMed Web of Science ®Google Scholar
• Scott LJ, Kim ES. Emicizumab-kxwh: First Global Approval. Drugs. 2018;78(2):269–74. doi:10.1007/s40265-018-0861-2. PMID: 29357074.
   PubMed Web of Science ®Google Scholar
• Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, Schmitt C, Jimenez-Yuste V, Kempton C, Dhalluin C. et al. Emicizumab prophylaxis in patients who have hemophilia a without inhibitors. N Engl J Med. 2018;379(9):811–22. doi:10.1056/NEJMoa1803550. PMID: 30157389.
   PubMed Web of Science ®Google Scholar
• Syed YY. Amivantamab: First Approval. Drugs. 2021;81(11):1349–53. doi:10.1007/s40265-021-01561-7. PMID: 34292533.
   PubMed Web of Science ®Google Scholar
• Zhou C, Tang KJ, Cho BC, Liu B, Paz-Ares L, Cheng S, Kitazono S, Thiagarajan M, Goldman JW, Sabari JK. et al. Amivantamab plus chemotherapy in NSCLC with EGFR Exon 20 insertions. N Engl J Med. 2023;389(22):2039–51. doi:10.1056/NEJMoa2306441. PMID: 37870976.
   PubMed Web of Science ®Google Scholar
• Dhillon S. Tebentafusp: First Approval. Drugs. 2022;82(6):703–10. doi:10.1007/s40265-022-01704-4. PMID: 35364798.
   PubMed Web of Science ®Google Scholar
• Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM. et al. Overall survival benefit with Tebentafusp in metastatic uveal melanoma. N Engl J Med. 2021;385(13):1196–206. doi:10.1056/NEJMoa2103485. PMID: 34551229.
   PubMed Web of Science ®Google Scholar
• Kang C. Mosunetuzumab: First Approval. Drugs. 2022;82(11):1229–34. doi:10.1007/s40265-022-01749-5. PMID: 35947358.
   PubMed Web of Science ®Google Scholar
• Budde LE, Sehn LH, Matasar M, Schuster SJ, Assouline S, Giri P, Kuruvilla J, Canales M, Dietrich S, Fay K. et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23:1055–65. doi:10.1016/S1470-2045(22)00335-7. PMID: 35803286.
   PubMed Web of Science ®Google Scholar
• Keam SJ. Cadonilimab: First Approval. Drugs. 2022;82(12):1333–39. doi:10.1007/s40265-022-01761-9. PMID: 35986837.
   PubMed Web of Science ®Google Scholar
• Frentzas S, Gan HK, Cosman R, Coward J, Tran B, Millward M, Zhou Y, Wang W, Xia D, Wang ZM. et al. A phase 1a/1b first-in-human study (COMPASSION-01) evaluating cadonilimab in patients with advanced solid tumors. Cell Rep Med. 2023;4(11):101242. doi:10.1016/j.xcrm.2023.101242. PMID: 37852261.
   PubMedGoogle Scholar
• Kang C. Teclistamab: First Approval. Drugs. 2022;82(16):1613–19. doi:10.1007/s40265-022-01793-1. PMID: 36352205.
   PubMed Web of Science ®Google Scholar
• Hindie E. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022;387:1721. doi:10.1056/NEJMc2211969. PMID: 36322859.
   PubMedGoogle Scholar
• Shirley M. Glofitamab: First Approval. Drugs. 2023;83(10):935–41. doi:10.1007/s40265-023-01894-5. PMID: 37285013.
   PubMed Web of Science ®Google Scholar
• Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, Khan C, Wrobel T, Offner F, Trneny M. et al. Glofitamab for relapsed or refractory diffuse large B-Cell lymphoma. N Engl J Med. 2022;387(24):2220–31. doi:10.1056/NEJMoa2206913. PMID: 36507690.
   PubMed Web of Science ®Google Scholar
• Frampton JE. Epcoritamab: First Approval. Drugs. 2023;83(14):1331–40. doi:10.1007/s40265-023-01930-4. PMID: 37597091.
   PubMed Web of Science ®Google Scholar
• Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, Do YR, Feldman T, Gasiorowski R, Jurczak W. et al. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell–Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. JCO. 2022;41(12):2238–47. doi:10.1200/JCO.22.01725. PMID: 36548927.
   PubMed Web of Science ®Google Scholar
• Chari A, Minnema MC, Berdeja JG, Oriol A, van de Donk N, Rodriguez-Otero P, Askari E, Mateos MV, Costa LJ, Caers J. et al. Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med. 2022;387(24):2232–44. doi:10.1056/NEJMoa2204591. PMID: 36507686.
   PubMed Web of Science ®Google Scholar
• Keam SJ. Talquetamab: First Approval. Drugs. 2023;83(15):1439–45. doi:10.1007/s40265-023-01945-x. PMID: 37792138.
   PubMed Web of Science ®Google Scholar
• Lesokhin AM, Tomasson MH, Arnulf B, Bahlis NJ, Miles Prince H, Niesvizky R, Rodrίguez-Otero P, Martinez-Lopez J, Koehne G, Touzeau C. et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29(9):2259–67. doi:10.1038/s41591-023-02528-9. PMID: 37582952.
   PubMed Web of Science ®Google Scholar
• Dhillon S. Elranatamab: First Approval. Drugs. 2023;83(17):1621–27. doi:10.1007/s40265-023-01954-w. PMID: 37924427.
   PubMed Web of Science ®Google Scholar
• Heier JS, Khanani AM, Quezada Ruiz C, Basu K, Ferrone PJ, Brittain C, Figueroa MS, Lin H, Holz FG, Patel V. et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet. 2022;399(10326):729–40. doi:10.1016/S0140-6736(22)00010-1. PMID: 35085502.
   PubMed Web of Science ®Google Scholar
• Shirley M. Faricimab: First Approval. Drugs. 2022;82(7):825–30. doi:10.1007/s40265-022-01713-3. PMID: 35474059.
   PubMed Web of Science ®Google Scholar
• Wykoff CC, Abreu F, Adamis AP, Basu K, Eichenbaum DA, Haskova Z, Lin H, Loewenstein A, Mohan S, Pearce IA. et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. Lancet. 2022;399(10326):741–55. doi:10.1016/S0140-6736(22)00018-6. PMID: 35085503.
   PubMed Web of Science ®Google Scholar
• Hattenbach LO, Abreu F, Arrisi P, Basu K, Danzig CJ, Guymer R, Haskova Z, Heier JS, Kotecha A, Liu Y. et al. BALATON and COMINO: phase III randomized clinical trials of Faricimab for retinal vein occlusion: study design and rationale. Ophthalmol Sci. 2023;3:100302. doi:10.1016/j.xops.2023.100302. PMID: 37810589.
   PubMedGoogle Scholar
• Tanaka Y, Kawanishi M, Nakanishi M, Yamasaki H, Takeuchi T. Efficacy and safety of the anti-TNF multivalent NANOBODY® compound ozoralizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: a 52-week result of a phase II/III study (OHZORA trial). Mod Rheumatol. 2023;33(5):883–90. doi:10.1093/mr/roac119. PMID: 36197757.
   PubMed Web of Science ®Google Scholar
• Tanaka Y, Kawanishi M, Nakanishi M, Yamasaki H, Takeuchi T. Efficacy and safety of anti-TNF multivalent NANOBODY® compound ‘ozoralizumab’ without methotrexate co-administration in patients with active rheumatoid arthritis: a 52-week result of phase III, randomised, open-label trial (NATSUZORA trial). Mod Rheumatol. 2023;33(5):875–82. doi:10.1093/mr/roac126. PMID: 36201360.
   PubMed Web of Science ®Google Scholar
• Keam SJ. Ozoralizumab: first approval. Drugs. 2023;83(1):87–92. doi:10.1007/s40265-022-01821-0. PMID: 36509938.
   PubMed Web of Science ®Google Scholar
• Dreier T, Baeuerle PA, Fichtner I, Grun M, Schlereth B, Lorenczewski G, Kufer P, Lutterbuse R, Riethmuller G, Gjorstrup P. et al. T cell costimulus-independent and very efficacious inhibition of tumor growth in mice bearing subcutaneous or leukemic human B cell lymphoma xenografts by a CD19-/CD3- bispecific single-chain antibody construct. J Immunol. 2003;170(8):4397–402. doi:10.4049/jimmunol.170.8.4397. PMID: 12682277.
   PubMed Web of Science ®Google Scholar
• Kufer P, Lutterbuse R, Baeuerle PA. A revival of bispecific antibodies. Trends Biotechnol. 2004;22:238–44. doi:10.1016/j.tibtech.2004.03.006. PMID: 15109810.
   PubMed Web of Science ®Google Scholar
• Berman DM, Bell JI. Redirecting polyclonal T cells against cancer with soluble T cell receptors. Clin Cancer Res. 2022;29(4):697–704. doi:10.1158/1078-0432.CCR-22-0028. PMID: 36255733.
   Web of Science ®Google Scholar
• Liddy N, Bossi G, Adams KJ, Lissina A, Mahon TM, Hassan NJ, Gavarret J, Bianchi FC, Pumphrey NJ, Ladell K. et al. Monoclonal TCR-redirected tumor cell killing. Nat Med. 2012;18(6):980–87. doi:10.1038/nm.2764. PMID: 22561687.
   PubMed Web of Science ®Google Scholar
• Ishiwatari-Ogata C, Kyuuma M, Ogata H, Yamakawa M, Iwata K, Ochi M, Hori M, Miyata N, Fujii FY. Ozoralizumab, a humanized anti-TNFα NANOBODY® compound, exhibits efficacy not only at the onset of Arthritis in a human TNF transgenic mouse but also during secondary failure of administration of an Anti-TNFα IgG. Front Immunol. 2022;13:853008. doi:10.3389/fimmu.2022.853008. PMID: 35273620.
   PubMed Web of Science ®Google Scholar
• Neijssen J, Cardoso RMF, Chevalier KM, Wiegman L, Valerius T, Anderson GM, Moores SL, Schuurman J, Parren P, Strohl WR. et al. Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET. J Biol Chem. 2021;296:100641. doi:10.1016/j.jbc.2021.100641. PMID: 33839159.
   PubMed Web of Science ®Google Scholar
• Pillarisetti K, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonca M, Majewski N, Nanjunda R. et al. Teclistamab is an active T cell–redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020;4(18):4538–49. doi:10.1182/bloodadvances.2020002393. PMID: 32956453.
   PubMed Web of Science ®Google Scholar
• Engelberts PJ, Hiemstra IH, de Jong B, Schuurhuis DH, Meesters J, Beltran Hernandez I, Oostindie SC, Neijssen J, van den Brink EN, Horbach GJ. et al. DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing. EBioMedicine. 2020;52:102625. doi:10.1016/j.ebiom.2019.102625. PMID: 31981978.
   PubMed Web of Science ®Google Scholar
• Verkleij CPM, Broekmans MEC, van Duin M, Frerichs KA, Kuiper R, de Jonge AV, Kaiser M, Morgan G, Axel A, Boominathan R. et al. Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma. Blood Adv. 2021;5:2196–215. doi:10.1182/bloodadvances.2020003805. PMID: 33890981.
   PubMed Web of Science ®Google Scholar
• Strop P, Ho WH, Boustany LM, Abdiche YN, Lindquist KC, Farias SE, Rickert M, Appah CT, Pascua E, Radcliffe T. et al. Generating bispecific human IgG1 and IgG2 antibodies from any antibody pair. J Mol Biol. 2012;420:204–19. doi:10.1016/j.jmb.2012.04.020. PMID: 22543237.
   PubMed Web of Science ®Google Scholar
• Panowski SH, Kuo TC, Zhang Y, Chen A, Geng T, Aschenbrenner L, Kamperschroer C, Pascua E, Chen W, Delaria K. et al. Preclinical efficacy and safety comparison of CD3 bispecific and ADC modalities targeting BCMA for the treatment of multiple myeloma. Mol Cancer Ther. 2019;18:2008–20. doi:10.1158/1535-7163.MCT-19-0007. PMID: 31434693.
   PubMed Web of Science ®Google Scholar
• Igawa T. Next generation antibody therapeutics using bispecific antibody technology. Yakugaku Zasshi. 2017;137:831–36. doi:10.1248/yakushi.16-00252-3. PMID: 28674296.
   PubMed Web of Science ®Google Scholar
• Kitazawa T, Igawa T, Sampei Z, Muto A, Kojima T, Soeda T, Yoshihashi K, Okuyama-Nishida Y, Saito H, Tsunoda H. et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia a model. Nat Med. 2012;18:1570–74. doi:10.1038/nm.2942. PMID: 23023498.
   PubMed Web of Science ®Google Scholar
• Sampei Z, Igawa T, Soeda T, Okuyama-Nishida Y, Moriyama C, Wakabayashi T, Tanaka E, Muto A, Kojima T, Kitazawa T. et al. Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PloS One. 2013;8(2):e57479. doi:10.1371/journal.pone.0057479. PMID: 23468998.
   PubMed Web of Science ®Google Scholar
• Sun LL, Ellerman D, Mathieu M, Hristopoulos M, Chen X, Li Y, Yan X, Clark R, Reyes A, Stefanich E. et al. Anti-CD20/CD3 T cell–dependent bispecific antibody for the treatment of B cell malignancies. Sci Transl Med. 2015;7(287):287ra270. doi:10.1126/scitranslmed.aaa4802. PMID: 25972002.
   Web of Science ®Google Scholar
• Regula JT, Lundh von Leithner P, Foxton R, Barathi VA, Gemmy Cheung CM, Bo Tun SB, Wey YS, Iwata D, Dostalek M, Moelleken J. et al. Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases. EMBO Mol Med. 2017;9(7):985. doi:10.15252/emmm.201707895. PMID: 28533211.
   PubMed Web of Science ®Google Scholar
• Bacac M, Colombetti S, Herter S, Sam J, Perro M, Chen S, Bianchi R, Richard M, Schoenle A, Nicolini V. et al. CD20-TCB with obinutuzumab pretreatment as next-generation treatment of hematologic malignancies. Clin Cancer Res. 2018;24:4785–97. doi:10.1158/1078-0432.CCR-18-0455. PMID: 29716920.
   PubMed Web of Science ®Google Scholar
• Pang X, Huang Z, Zhong T, Zhang P, Wang ZM, Xia M, Li B. Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity. MAbs. 2023;15(1):2180794. doi:10.1080/19420862.2023.2180794. PMID: 36872527.
   PubMed Web of Science ®Google Scholar
• Gramer MJ, van den Bremer ET, van Kampen MD, Kundu A, Kopfmann P, Etter E, Stinehelfer D, Long J, Lannom T, Noordergraaf EH. et al. Production of stable bispecific IgG1 by controlled Fab-arm exchange: scalability from bench to large-scale manufacturing by application of standard approaches. MAbs. 2013;5(6):962–73. doi:10.4161/mabs.26233. PMID: 23995617.
   PubMed Web of Science ®Google Scholar
• Labrijn AF, Meesters JI, de Goeij BE, van den Bremer ET, Neijssen J, van Kampen MD, Strumane K, Verploegen S, Kundu A, Gramer MJ. et al. Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange. Proc Natl Acad Sci U S A. 2013;110:5145–50. doi:10.1073/pnas.1220145110. PMID: 23479652.
   PubMed Web of Science ®Google Scholar
• Ridgway JB, Presta LG, Carter P. ‘Knobs-into-holes’ engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng. 1996;9(7):617–21. doi:10.1093/protein/9.7.617. PMID: 8844834.
   PubMedGoogle Scholar
• Zhu Z, Presta LG, Zapata G, Carter P. Remodeling domain interfaces to enhance heterodimer formation. Protein Sci. 1997;6:781–88. doi:10.1002/pro.5560060404. PMID: 9098887.
   PubMed Web of Science ®Google Scholar
• Regula JT, Imhof-Jung S, Molhoj M, Benz J, Ehler A, Bujotzek A, Schaefer W, Klein C. Variable heavy–variable light domain and Fab-arm CrossMabs with charged residue exchanges to enforce correct light chain assembly. Protein Eng Des Sel. 2018;31(7–8):289–99. doi:10.1093/protein/gzy021. PMID: 30169707.
   PubMed Web of Science ®Google Scholar
• Schaefer W, Regula JT, Bahner M, Schanzer J, Croasdale R, Durr H, Gassner C, Georges G, Kettenberger H, Imhof-Jung S. et al. Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies. Proc Natl Acad Sci U S A. 2011;108:11187–92. doi:10.1073/pnas.1019002108. PMID: 21690412.
   PubMed Web of Science ®Google Scholar
• Surowka M, Schaefer W, Klein C. Ten Years in the making: application of CrossMab technology for the development of therapeutic bispecific antibodies and antibody fusion proteins. MAbs. 2021;13(1):1967714. doi:10.1080/19420862.2021.1967714. PMID: 34491877.
   PubMed Web of Science ®Google Scholar
• van de Donk N, Zweegman S. T-cell-engaging bispecific antibodies in cancer. Lancet. 2023;402(10396):142–58. doi:10.1016/S0140-6736(23)00521-4. PMID: 37271153.
   PubMed Web of Science ®Google Scholar
• Arvedson T, Bailis JM, Britten CD, Klinger M, Nagorsen D, Coxon A, Egen JG, Martin F. Targeting solid tumors with bispecific T cell engager immune therapy. Annu Rev Cancer Biol. 2022;6(1):17–34. doi:10.1146/annurev-cancerbio-070620-104325. PMID: WOS:000789891800002.
   Google Scholar
• Lenting PJ, Denis CV, Christophe OD. Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how does it actually compare to factor VIII? Blood. 2017;130(23):2463–68. doi:10.1182/blood-2017-08-801662. PMID: 29042366.
   PubMed Web of Science ®Google Scholar
• Fauvel B, Yasri A. Antibodies directed against receptor tyrosine kinases: current and future strategies to fight cancer. MAbs. 2014;6(4):838–51. doi:10.4161/mabs.29089. PMID: 24859229.
   PubMed Web of Science ®Google Scholar
• Sharma P, Goswami S, Raychaudhuri D, Siddiqui BA, Singh P, Nagarajan A, Liu J, Subudhi SK, Poon C, Gant KL. et al. Immune checkpoint therapy—current perspectives and future directions. Cell. 2023;186(8):1652–69. doi:10.1016/j.cell.2023.03.006. PMID: 37059068.
   PubMed Web of Science ®Google Scholar
• Cao Y, Langer R, Ferrara N. Targeting angiogenesis in oncology, ophthalmology and beyond. Nat Rev Drug Discov. 2023;22(6):476–95. doi:10.1038/s41573-023-00671-z. PMID: 37041221.
   PubMed Web of Science ®Google Scholar
• Sharma A, Kumar N, Kuppermann BD, Bandello F, Loewenstein A. Faricimab: expanding horizon beyond VEGF. Eye (Lond). 2020;34(5):802–04. doi:10.1038/s41433-019-0670-1. PMID: 31695160.
   PubMed Web of Science ®Google Scholar
• Foxton RH, Uhles S, Gruner S, Revelant F, Ullmer C. Efficacy of simultaneous VEGF-A/ANG-2 neutralization in suppressing spontaneous choroidal neovascularization. EMBO Mol Med. 2019;11(5). doi:10.15252/emmm.201810204. PMID: 31040126.
   Web of Science ®Google Scholar
• Herpers B, Eppink B, James MI, Cortina C, Canellas-Socias A, Boj SF, Hernando-Momblona X, Glodzik D, Roovers RC, van de Wetering M. et al. Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors. Nat Cancer. 2022;3(4):418–36. doi:10.1038/s43018-022-00359-0. PMID: 35469014.
   PubMedGoogle Scholar
• Schram AM, Odintsov I, Espinosa-Cotton M, Khodos I, Sisso WJ, Mattar MS, Lui AJW, Vojnic M, Shameem SH, Chauhan T. et al. Zenocutuzumab, a HER2xHER3 Bispecific Antibody, Is Effective Therapy for Tumors Driven by NRG1 Gene Rearrangements. Cancer Discov. 2022;12:1233–47. doi:10.1158/2159-8290.CD-21-1119. PMID: 35135829.
   PubMed Web of Science ®Google Scholar
• Weisser NE, Sanches M, Escobar-Cabrera E, O’Toole J, Whalen E, Chan PWY, Wickman G, Abraham L, Choi K, Harbourne B. et al. An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity. Nat Commun. 2023;14(1):1394. doi:10.1038/s41467-023-37029-3. PMID: 36914633.
   PubMed Web of Science ®Google Scholar
• Meric-Bernstam F, Beeram M, Hamilton E, Oh DY, Hanna DL, Kang YK, Elimova E, Chaves J, Goodwin R, Lee J. et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study. Lancet Oncol. 2022;23:1558–70. doi:10.1016/S1470-2045(22)00621-0. PMID: 36400106.
   PubMed Web of Science ®Google Scholar
• Harding JJ, Fan J, Oh DY, Choi HJ, Kim JW, Chang HM, Bao L, Sun HC, Macarulla T, Xie F. et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncol. 2023;24:772–82. doi:10.1016/S1470-2045(23)00242-5. PMID: 37276871.
   PubMed Web of Science ®Google Scholar
• Crescioli S, Kaplon H, Chenoweth A, Wang L, Visweswaraiah J, Reichert JM. Antibodies to watch in 2024. MAbs. 2024;16(1):2297450. doi:10.1080/19420862.2023.2297450. PMID: 38178784.
   PubMed Web of Science ®Google Scholar
• Dumontet C, Reichert JM, Senter PD, Lambert JM, Beck A. Antibody–drug conjugates come of age in oncology. Nat Rev Drug Discov. 2023;22(8):641–61. doi:10.1038/s41573-023-00709-2. PMID: 37308581.
   PubMed Web of Science ®Google Scholar
• Tsuchikama K, Anami Y, Ha SYY, Yamazaki CM. Exploring the next generation of antibody-drug conjugates. Nat Rev Clin Oncol. 2024. doi:10.1038/s41571-023-00850-2. PMID: 38191923.
   PubMed Web of Science ®Google Scholar
• Gu Y, Wang Z, Wang Y. Bispecific antibody drug conjugates: Making 1+1>2. Acta Pharm Sin B. 2024. doi:10.1016/j.apsb.2024.01.009.
   Google Scholar
• Perez Bay AE, Faulkner D, DaSilva JO, Young TM, Yang K, Giurleo JT, Ma D, Delfino FJ, Olson WC, Thurston G. et al. A bispecific METxMET antibody–drug conjugate with cleavable linker is processed in recycling and late endosomes. Mol Cancer Ther. 2023;22(3):357–70. doi:10.1158/1535-7163.MCT-22-0414. PMID: 36861363.
   PubMed Web of Science ®Google Scholar
• Bannerji R, Arnason JE, Advani RH, Brown JR, Allan JN, Ansell SM, Barnes JA, O’Brien SM, Chavez JC, Duell J. et al. Odronextamab, a human CD20×CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Lancet Haematol. 2022;9(5):e327–39. doi:10.1016/S2352-3026(22)00072-2. PMID: 35366963.
   PubMed Web of Science ®Google Scholar
• Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS. et al. Tarlatamab for patients with Previously treated small-cell lung cancer. N Engl J Med. 2023;389(22):2063–75. doi:10.1056/NEJMoa2307980. PMID: 37861218.
   PubMed Web of Science ®Google Scholar
• Paz-Ares L, Champiat S, Lai WV, Izumi H, Govindan R, Boyer M, Hummel HD, Borghaei H, Johnson ML, Steeghs N. et al. Tarlatamab, a first-in-class DLL3-targeted bispecific T cell engager, in recurrent small-cell lung cancer: an open-label, phase 1 study. JCO. 2023;41(16):2893–903. doi:10.1200/JCO.22.02823. PMID: 36689692.
   PubMed Web of Science ®Google Scholar
• Kelly WK, Danila DC, Lin CC, Lee JL, Matsubara N, Ward PJ, Armstrong AJ, Pook D, Kim M, Dorff TB. et al. Xaluritamig, a STEAP1 × CD3 XmAb 2+1 immune therapy for metastatic castration-resistant prostate cancer: results from dose exploration in a first-in-human study. Cancer Discov. 2023;14(1):OF1–14. doi:10.1158/2159-8290.CD-23-0964. PMID: 37861461.
   Google Scholar
• Nolan-Stevaux O, Li C, Liang L, Zhan J, Estrada J, Osgood T, Li F, Zhang H, Case R, Murawsky CM. et al. AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity Against Prostate Cancer. Cancer Discov. 2023. doi:10.1158/2159-8290.CD-23-0984. PMID: 37861452.
   Google Scholar
• Panchal A, Seto P, Wall R, Hillier BJ, Zhu Y, Krakow J, Datt A, Pongo E, Bagheri A, Chen TT. et al. COBRA™: a highly potent conditionally active T cell engager engineered for the treatment of solid tumors. MAbs. 2020;12(1):1792130. doi:10.1080/19420862.2020.1792130. PMID: 32684124.
   PubMed Web of Science ®Google Scholar
• Geiger M, Stubenrauch KG, Sam J, Richter WF, Jordan G, Eckmann J, Hage C, Nicolini V, Freimoser-Grundschober A, Ritter M. et al. Protease-activation using anti-idiotypic masks enables tumor specificity of a folate receptor 1-T cell bispecific antibody. Nat Commun. 2020;11(1):3196. doi:10.1038/s41467-020-16838-w. PMID: 32581215.
   PubMed Web of Science ®Google Scholar
• Dettling DE, Kwok E, Quach L, Datt A, Degenhardt JD, Panchal A, Seto P, Krakow JL, Wall R, Hillier BJ. et al. Regression of EGFR positive established solid tumors in mice with the conditionally active T cell engager TAK-186. J Immunother Cancer. 2022;10(6):e004336. doi:10.1136/jitc-2021-004336. PMID: 35728872.
   PubMed Web of Science ®Google Scholar
• Boustany LM, LaPorte SL, Wong L, White C, Vinod V, Shen J, Yu W, Koditek D, Winter MB, Moore SJ. et al. A probody T cell–engaging bispecific antibody targeting EGFR and CD3 inhibits colon cancer growth with limited toxicity. Cancer Res. 2022;82(22):4288–98. doi:10.1158/0008-5472.CAN-21-2483. PMID: 36112781.
   PubMed Web of Science ®Google Scholar
• Cattaruzza F, Nazeer A, To M, Hammond M, Koski C, Liu LY, Pete Yeung V, Rennerfeldt DA, Henkensiefken A, Fox M. et al. Precision-activated T-cell engagers targeting HER2 or EGFR and CD3 mitigate on-target, off-tumor toxicity for immunotherapy in solid tumors. Nat Cancer. 2023;4(4):485–501. doi:10.1038/s43018-023-00536-9. PMID: 36997747.
   PubMedGoogle Scholar
• Claus C, Ferrara C, Xu W, Sam J, Lang S, Uhlenbrock F, Albrecht R, Herter S, Schlenker R, Husser T. et al. Tumor-targeted 4-1BB agonists for combination with T cell bispecific antibodies as off-the-shelf therapy. Sci Transl Med. 2019;11(496):11. doi:10.1126/scitranslmed.aav5989. PMID: 31189721.
   Web of Science ®Google Scholar
• Skokos D, Waite JC, Haber L, Crawford A, Hermann A, Ullman E, Slim R, Godin S, Ajithdoss D, Ye X. et al. A class of costimulatory CD28-bispecific antibodies that enhance the antitumor activity of CD3-bispecific antibodies. Sci Transl Med. 2020;12(525):12. doi:10.1126/scitranslmed.aaw7888. PMID: 31915305.
   Web of Science ®Google Scholar
• Berezhnoy A, Sumrow BJ, Stahl K, Shah K, Liu D, Li J, Hao SS, De Costa A, Kaul S, Bendell J. et al. Development and preliminary clinical activity of PD-1-Guided CTLA-4 blocking bispecific DART molecule. Cell Rep Med. 2020;1:100163. doi:10.1016/j.xcrm.2020.100163. PMID: 33377134.
   PubMedGoogle Scholar
• Dovedi SJ, Elder MJ, Yang C, Sitnikova SI, Irving L, Hansen A, Hair J, Jones DC, Hasani S, Wang B. et al. Design and efficacy of a monovalent bispecific PD-1/CTLA4 antibody that enhances CTLA4 blockade on PD-1(+) activated T cells. Cancer Discov. 2021;11(5):1100–17. doi:10.1158/2159-8290.CD-20-1445. PMID: 33419761.
   PubMed Web of Science ®Google Scholar
• Luke JJ, Patel MR, Blumenschein GR, Hamilton E, Chmielowski B, Ulahannan SV, Connolly RM, Santa-Maria CA, Wang J, Bahadur SW. et al. The PD-1- and LAG-3-targeting bispecific molecule tebotelimab in solid tumors and hematologic cancers: a phase 1 trial. Nat Med. 2023;29(11):2814–24. doi:10.1038/s41591-023-02593-0. PMID: 37857711.
   PubMedGoogle Scholar
• Wang L, Luo Y, Ren S, Zhang Z, Xiong A, Su C, Zhou J, Yu X, Hu Y, Zhang X. et al. A phase 1b study of ivonescimab, a programmed cell death protein-1 and vascular endothelial growth factor bispecific antibody, as first- or second-line therapy for advanced or metastatic immunotherapy-naive NSCLC. J Thorac Oncol. 2023. doi:10.1016/j.jtho.2023.10.014. PMID: 37879536.
   Google Scholar
• Whalen KA, Rakhra K, Mehta NK, Steinle A, Michaelson JS, Baeuerle PA. Engaging natural killer cells for cancer therapy via NKG2D, CD16A and other receptors. MAbs. 2023;15(1):2208697. doi:10.1080/19420862.2023.2208697. PMID: 37165468.
   PubMed Web of Science ®Google Scholar
• Mensurado S, Blanco-Dominguez R, Silva-Santos B. The emerging roles of γδ T cells in cancer immunotherapy. Nat Rev Clin Oncol. 2023;20(3):178–91. doi:10.1038/s41571-022-00722-1. PMID: 36624304.
   PubMed Web of Science ®Google Scholar
• Sewnath CA, Behrens LM, van Egmond M. Targeting myeloid cells with bispecific antibodies as novel immunotherapies of cancer. Expert Opin Biol Th. 2022;22(8):983–95. doi:10.1080/14712598.2022.2098675. PMID: WOS:000828289800001.
   PubMed Web of Science ®Google Scholar
• Dickopf S, Buldun C, Vasic V, Georges G, Hage C, Mayer K, Forster M, Wessels U, Stubenrauch KG, Benz J. et al. Prodrug-Activating Chain Exchange (PACE) converts targeted prodrug derivatives to functional bi- or multispecific antibodies. Biol Chem. 2022;403:495–508. doi:10.1515/hsz-2021-0401. PMID: 35073465.
   PubMed Web of Science ®Google Scholar
• Banaszek A, Bumm TGP, Nowotny B, Geis M, Jacob K, Wolfl M, Trebing J, Kucka K, Kouhestani D, Gogishvili T. et al. On-target restoration of a split T cell-engaging antibody for precision immunotherapy. Nat Commun. 2019;10(1):5387. doi:10.1038/s41467-019-13196-0. PMID: 31772172.
   PubMedGoogle Scholar
• Lucchi R, Bentanachs J, Oller-Salvia B. The masking game: design of activatable antibodies and mimetics for selective therapeutics and cell control. ACS Cent Sci. 2021;7(5):724–38. doi:10.1021/acscentsci.0c01448. PMID: 34079893.
   PubMed Web of Science ®Google Scholar
• Wells JA, Kumru K. Extracellular targeted protein degradation: an emerging modality for drug discovery. Nat Rev Drug Discov. 2023;23(2):126–40. doi:10.1038/s41573-023-00833-z. PMID: 38062152.
   PubMed Web of Science ®Google Scholar
• Yen M, Ren J, Liu Q, Glassman CR, Sheahan TP, Picton LK, Moreira FR, Rustagi A, Jude KM, Zhao X. et al. Facile discovery of surrogate cytokine agonists. Cell. 2022;185(8):1414–30 e1419. doi:10.1016/j.cell.2022.02.025. PMID: 35325595.
   PubMed Web of Science ®Google Scholar
• Harris KE, Lorentsen KJ, Malik-Chaudhry HK, Loughlin K, Basappa HM, Hartstein S, Ahmil G, Allen NS, Avanzino BC, Balasubramani A. et al. A bispecific antibody agonist of the IL-2 heterodimeric receptor preferentially promotes in vivo expansion of CD8 and NK cells. Sci Rep. 2021;11(1):10592. doi:10.1038/s41598-021-90096-8. PMID: 34011961.
   PubMed Web of Science ®Google Scholar
• Zhao P, Zhang N, An Z. Engineering antibody and protein therapeutics to cross the blood–brain barrier. Antib Ther. 2022;5(4):311–31. doi:10.1093/abt/tbac028. PMID: 36540309.
   PubMedGoogle Scholar
• Grimm HP, Schumacher V, Schäfer M, Imhof-Jung S, Freskgård PO, Brady K, Hofmann C, Rüger P, Schlothauer T, Göpfert U. et al. Delivery of the Brainshuttle™ amyloid-beta antibody fusion trontinemab to non-human primate brain and projected efficacious dose regimens in humans. MAbs. 2023;15(1):2261509. doi:10.1080/19420862.2023.2261509. PMID: WOS:001084988100001.
   PubMed Web of Science ®Google Scholar