Abstract 2734: Novel CTLA4 antibodies demonstrate potent antitumor activity in a humanized mouse model

Abstract

Abstract CTLA4 (cytotoxic T-lymphocyte-associated protein 4), is a member of the immunoglobulin superfamily. It is expressed in T cells upon activation and transmits an inhibitor signal to T cells. Also, it is constitutively expressed in regulatory T cells (Tregs) which is associated with their immunosuppressive phenotype. CTLA4 is homologous to the co-stimulatory protein CD28, and both receptor binds to CD80 and CD86. Cancer cells can be recognized and destructed by the host's immune system. In this setting, CTLA4 functions as a brake to dampen anti-tumor T cell responses, which promote cancer progression. Antibodies targeting CTLA4 was expected to subvert T cell inhibition. Moreover, regulatory T cells residing in the tumor microenvironment can be killed by anti-CTLA4 antibody since these cells have higher expression level of CTLA4 comparing with the activated T cells. Yervoy, an anti-CTLA4 antibody, was the first FDA-approved antibody targeting the immune checkpointfamily, and it protects a fraction of cancer patients when either used alone or in combination with other drugs. We asked whether the efficacy of anti-CTLA4 antibodies could be evaluated in humanized mouse models. And if so, whether we can use in vivo assay to guide the development of potent antibodies targeting CTLA4. Here, we describe that using the platform established at Biocytogen, we successfully discovered two antibodies whose efficacy is equivalent or exceed that of Yervoy. The clinical evaluation of these new entities are wanted. Citation Format: Jie Xiang, Yanan Guo, Yuelei Shen, Benny Yang. Novel CTLA4 antibodies demonstrate potent antitumor activity in a humanized mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2734.