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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01994

Conventional and Chemically Programmed Asymmetric Bispecific Antibodies Targeting Folate Receptor 1

 Junpeng Qi1, David Hymel2, Christopher G. Nelson2,  Terrence R. Burke2 and  Christoph Rader3*
  • 1Department of Immunology and Microbiology, The Scripps Research Institute, United States
  • 2National Cancer Institute at Frederick, United States
  • 3Department of Immunology and Microbiology, The Scripps Research Institute, United States

T-cell engaging bispecific antibodies (biAbs) can mediate potent and specific tumor cell eradication in liquid cancers. Substantial effort has been invested in expanding this concept to solid cancers. To explore their utility in the treatment of ovarian cancer, we built a set of asymmetric biAbs in IgG1-like format that bind CD3 on T cells with a conventional scFv arm and folate receptor 1 (FOLR1) on ovarian cancer cells with a conventional or a chemically programmed Fab arm. For avidity engineering, we also built an asymmetric biAb format with a tandem Fab arm. We show that both conventional and chemically programmed CD3 × FOLR1 biAbs exert specific in vitro and in vivo cytotoxicity toward FOLR1-expressing ovarian cancer cells by recruiting and activating T cells. While the conventional T-cell engaging biAb was curative in an aggressive mouse model of human ovarian cancer, the potency of the chemically programmed biAb was significantly boosted by avidity engineering. Both conventional and chemically programmed CD3 × FOLR1 biAbs warrant further investigation for ovarian cancer immunotherapy.

Keywords: Bispecific antibodies., Catalytic antibodies, Folate, FOLR1, CD3, ovarian cancer

Received: 22 Apr 2019; Accepted: 07 Aug 2019.

Edited by:

Jose A. Garcia-Sanz, Spanish National Research Council (CSIC), Spain

Reviewed by:

Jyothi Thyagabhavan Mony, Washington University in St. Louis, United States
Diego Ellerman, Genentech, Inc., United States  

Copyright: © 2019 Qi, Hymel, Nelson, Burke and Rader. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Christoph Rader, The Scripps Research Institute, Department of Immunology and Microbiology, Jupiter, United States, crader@scripps.edu