Abstract 3265: Anti-GITR agonist antibody for cancer immunotherapy

Abstract

Abstract Glucocorticoid-induced TNFR-related (GITR) is a gene coding for a member of the TNF receptor superfamily. GITR is expressed at low levels on resting responder T lymphocytes and is up-regulated in T regulatory cells (Treg cells) and in activated T cells. GITR agonist which upregulated co-stimulatory signal to T cells or inhibition of Treg induced suppression which reverts Treg proliferation, is likely to enhance immunity in response to infection and tumor immunity. Therefore, GITR is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule. In this study, various types of GITR immunogens, including gene, protein and cell line, are used for H2L2 mice immunization. Then we generate and characterize panels of anti-GITR monoclonal antibodies which not only could specifically bind to human GITR, but also show cross-reactivity to cyno GITR. Such anti-GITR antibody can increase the expression of NF-κB gene by cross-linking by anti-Fab, and induce the release of INF-γ from T cell. In harsh pH or temperature condition, the anti-GITR antibody can keep the stability. And at high concentration, the viscosity of the anti-GITR antibody is good. Moreover, in vivo study showed that the anti-GITR antibody can effectively inhibit tumor growth. Above results demonstrated that the anti-GITR antibody is expected to develop further for clinical study single or combine with other immune checkpoint antibody. Citation Format: Teddy Yang, Ken Dai, Dongxu Wang, Qianqian Qi, Hu Liu. Anti-GITR agonist antibody for cancer immunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3265.