A Novel Bispecific Antibody against Human CD3 and Ephrin Receptor A10 for Breast Cancer TherapyReportar como inadecuado

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Ephrin receptor A10 EphA10, a transmembrane receptor that binds to ephrin, is a newly identified breast cancer marker protein that has also been detected in HER2-negative tissue. In this study, we report creation of a novel bispecific antibody BsAb binding both EphA10 and CD3, thereby forming a bridge between antigens expressed on both tumor and immune cells and promoting recognition of tumor cells by immune cells and redirection of cytotoxic T cells CTL. This BsAb EphA10-CD3 was expressed in supernatants of BsAb gene-transfected cells as monomeric and dimeric molecules. Redirected T-cell lysis was observed when monomeric and dimeric BsAb were added to EphA10-overexpressing tumor cells in vitro. Furthermore, dimeric BsAb EphA10-CD3 was more cytotoxic than monomeric BsAb, with efficient tumor cell lysis elicited by lower concentrations ≤10−1 μg-mL and a lower effector to target E-T cell ratio E-T = 2.5. Dimeric BsAb EphA10-CD3 also showed significant anti-tumor effects in human xenograft mouse models. Together, these results revealed opportunities to redirect the activity of CTL towards tumor cells that express EphA10 using the BsAb EphA10-CD3, which could be tested in future clinical trials as a novel and potent therapeutic for breast cancer tumors.

Autor: Shintaro Taki , Haruhiko Kamada , Masaki Inoue, Kazuya Nagano, Yohei Mukai, Kazuma Higashisaka, Yasuo Yoshioka, Yasuo Tsutsumi, S

Fuente: http://plos.srce.hr/


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