A novel conditional active biologic anti-EpCAM x anti-CD3 bispecific antibody with synergistic tumor selectivity for cancer immunotherapy

References

• Herreros-Pomares A, Aguilar-Gallardo C, Calabuig-Farinas S, Sirera R, Jantus-Lewintre E, Camps C. EpCAM duality becomes this molecule in a new Dr. Jekyll and Mr. Hyde tale. Crit Rev Oncol Hematol. 2018;126:52–14. doi:10.1016/j.critrevonc.2018.03.006.
   PubMed Web of Science ®Google Scholar
• Armstrong A, Eck SL. EpCAM: a new therapeutic target for an old cancer antigen. Cancer Biol Ther. 2003;2:320–26. doi:10.4161/cbt.2.4.451.
   PubMed Web of Science ®Google Scholar
• Spizzo G, Fong D, Wurm M, Ensinger C, Obrist P, Hofer C, Mazzoleni G, Gastl G, Went P. EpCAM expression in primary tumour tissues and metastases: an immunohistochemical analysis. J Clin Pathol. 2011;64:415–20. doi:10.1136/jcp.2011.090274.
   PubMed Web of Science ®Google Scholar
• Liu Y, Wang Y, Sun S, Chen Z, Xiang S, Ding Z, Huang Z, Zhang B. Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside. Exp Hematol Oncol. 2022;11:97. doi:10.1186/s40164-022-00352-4.
   PubMed Web of Science ®Google Scholar
• Przepiorka D, Ko CW, Deisseroth A, Yancey CL, Candau-Chacon R, Chiu HJ, Gehrke BJ, Gomez-Broughton C, Kane RC, Kirshner S. et al. FDA Approval: Blinatumomab. Clin Cancer Res. 2015;21(18):4035–9. doi:10.1158/1078-0432.CCR-15-0612.
   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. J Clin Oncol. 2023;41(12):2238–47. doi:10.1200/JCO.22.01725.
   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(8):1055–65. doi:10.1016/S1470-2045(22)00335-7.
   PubMed Web of Science ®Google Scholar
• Kiewe P, Hasmuller S, Kahlert S, Heinrigs M, Rack B, Marme A, Korfel A, Jäger M, Lindhofer H, Sommer H. et al. Phase I trial of the trifunctional Anti-HER2 × Anti-CD3 antibody ertumaxomab in metastatic breast cancer. Clin Cancer Res. 2006;12:3085–91. doi:10.1158/1078-0432.CCR-05-2436.
   PubMed Web of Science ®Google Scholar
• Seimetz D, Lindhofer H, Bokemeyer C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010;36:458–67. doi:10.1016/j.ctrv.2010.03.001.
   PubMed Web of Science ®Google Scholar
• Mau-Sørensen M, Dittrich C, Dienstmann R, Lassen U, Büchler W, Martinius H, Tabernero J. A phase I trial of intravenous catumaxomab: a bispecific monoclonal antibody targeting EpCAM and the T cell coreceptor CD3. Cancer Chemother Pharmacol. 2015;75:1065–73. doi:10.1007/s00280-015-2728-5.
   PubMed Web of Science ®Google Scholar
• Cioffi M, Dorado J, Baeuerle PA, Heeschen C. EpCAM/CD3-Bispecific T-cell engaging antibody MT110 eliminates primary human pancreatic cancer stem cells. Clin Cancer Res. 2012;18(2):465–74. doi:10.1158/1078-0432.CCR-11-1270.
   PubMed Web of Science ®Google Scholar
• English DP, Bellone S, Schwab CL, Roque DM, Lopez S, Bortolomai I, Cocco E, Bonazzoli E, Chatterjee S, Ratner E. et al. Solitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy-resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo. Cancer. 2015;121(3):403–12. doi:10.1002/cncr.29062.
   PubMed Web of Science ®Google Scholar
• Kebenko M, Goebeler ME, Wolf M, Hasenburg A, Seggewiss-Bernhardt R, Ritter B, Rautenberg B, Atanackovic D, Kratzer A, Rottman JB. et al. A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors. Oncoimmunology. 2018;7:e1450710. doi:10.1080/2162402X.2018.1450710.
   PubMed Web of Science ®Google Scholar
• Chang HW, Frey G, Liu H, Xing C, Steinman L, Boyle WJ, Short JM. Generating tumor-selective conditionally active biologic anti-CTLA4 antibodies via protein-associated chemical switches. Proc Natl Acad Sci U S A. 2021;118. doi:10.1073/pnas.2020606118.
   Web of Science ®Google Scholar
• Chen M, Chen C, Shen Z, Zhang X, Chen Y, Lin F, Ma X, Zhuang C, Mao Y, Gan H. et al. Extracellular pH is a biomarker enabling detection of breast cancer and liver cancer using CEST MRI. Oncotarget. 2017;8(28):45759–67. doi:10.18632/oncotarget.17404.
   PubMedGoogle Scholar
• Liu X, Deng J, Yuan Y, Chen W, Sun W, Wang Y, Huang H, Liang B, Ming T, Wen J. et al. Advances in Trop2-targeted therapy: novel agents and opportunities beyond breast cancer. Pharmacology & Therapeutics. 2022;239:108296. doi:10.1016/j.pharmthera.2022.108296.
   PubMed Web of Science ®Google Scholar
• Linke R, Klein A, Seimetz D. Catumaxomab: clinical development and future directions. Mabs-austin. 2010;2(2):129–36. doi:10.4161/mabs.2.2.11221.
   PubMed Web of Science ®Google Scholar
• Baeuerle PA, Wesche H. T-cell-engaging antibodies for the treatment of solid tumors: challenges and opportunities. Curr Opin Oncol. 2022;34(5):552–8. doi:10.1097/CCO.0000000000000869.
   PubMed Web of Science ®Google Scholar
• Dreher MR, Liu W, Michelich CR, Dewhirst MW, Yuan F, Chilkoti A. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J Natl Cancer Inst. 2006;98(5):335–44. doi:10.1093/jnci/djj070.
   PubMed Web of Science ®Google Scholar
• Goebeler ME, Bargou RC. T cell-engaging therapies - BiTEs and beyond. Nat Rev Clin Oncol. 2020;17:418–34. doi:10.1038/s41571-020-0347-5.
   PubMed Web of Science ®Google Scholar
• Saber H, Del Valle P, Ricks TK, Leighton JK. An FDA oncology analysis of CD3 bispecific constructs and first-in-human dose selection. Regul Toxicol Pharmacol. 2017;90:144–52. doi:10.1016/j.yrtph.2017.09.001.
   PubMed Web of Science ®Google Scholar
• Shanshal M, Caimi PF, Adjei AA, Ma WW. T-Cell engagers in solid cancers—Current landscape and future directions. Cancers Basel. 2023;15:15. doi:10.3390/cancers15102824.
   Web of Science ®Google Scholar
• Spiess C, Merchant M, Huang A, Zheng Z, Yang NY, Peng J, Ellerman D, Shatz W, Reilly D, Yansura DG. et al. Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies. Nat Biotechnol. 2013;31(8):753–8. doi:10.1038/nbt.2621.
   PubMed Web of Science ®Google Scholar
• Bolt S, Routledge E, Lloyd I, Chatenoud L, Pope H, Gorman SD, Clark M, Waldmann H. The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties. Eur J Immunol. 1993;23:403–11. doi:10.1002/eji.1830230216.
   PubMed Web of Science ®Google Scholar
• Wang X, Mathieu M, Brezski RJ. IgG fc engineering to modulate antibody effector functions. Protein Cell. 2018;9(1):63–73. doi:10.1007/s13238-017-0473-8.
   PubMed Web of Science ®Google Scholar
• Kumari R, Feuer G, Bourre L. Humanized mouse models for Immuno-oncology drug discovery. Curr Protoc. 2023;3:e852. doi:10.1002/cpz1.852.
   PubMedGoogle Scholar
• De La Rochere P, Guil-Luna S, Decaudin D, Azar G, Sidhu SS, Piaggio E. Humanized mice for the study of immuno-oncology. Trends Immunol. 2018;39(9):748–63. doi:10.1016/j.it.2018.07.001.
   PubMed Web of Science ®Google Scholar