Discover Potent And Functional Human Antibodies Against A New B7-Family Member Target For Cancer Immunotherapy.

Abstract Immunotherapeutics targeting immune checkpoints such as PD1/PD-L1 and CTLA4 offer effective treatment alternatives to the traditional cancer therapies. However, a considerable proportion of patients remain unresponsive to treatment indicating that a more complex immune suppressive tumor microenvironment is involved. Developing novel immune checkpoint inhibitors for combination with current approaches can provide more efficient therapies and expanded indications. A novel B7 family member B7y was recently reported to be highly expressed on a variety of human cancers such as colon, pancreas, breast, bladder, lung cancers and associated with metastatic disease and poor survival. Its co-inhibitory function makes it a new checkpoint and candidate for cancer immunotherapy other than PD-L1 or other immune checkpoints. Here we report the development of functional antibodies targeting this novel B7 family member with potent anti-tumor effect. Generated with H2L2 Harbour Mice® platform, these fully human anti-B7y antibodies specifically bind to cell lines that over-express human or cynomolgus B7y, as well as human tumor cell lines that express endogenous B7y, with high selectivity against other B7 family members. Antibodies that blocked the interaction between B7y and its receptors potently promoted T cell activation in vitro dependent on B7y expression on APC cells. Furthermore, these antibodies in ADCC null versions showed potent anti-tumor activity in humanized murine tumor model. In conclusion, we generated highly potent human antibodies targeting the new immune checkpoint B7 family member and showed good anti-tumor efficacy. Anti-B7y antibody presents a promising novel anti-tumor agent as monotherapy and/or combination therapy with currently established IO agents. Citation Format: Xiaodong Wu, Yongqiang Wang, Xiaocheng Lv, Fei Chen, Yun He, Jiuqiao Zhao, Yiping Rong. Discover potent and functional human antibodies against a new B7-family member target for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1603.