Recently, checkpoint blockade-mediated immune reinvigoration acts as potential strategies to cure cancer. In addition to checkpoint blockade, a number of studies have shown that immune co-stimulators also act as crucial players in the immunotherapy. Inducible co-stimulator (ICOS), a homodimeric protein that belongs to CD28 superfamily, is expressed on activated T-cells and resting memory T-cells. Upon stimulation, ICOS and its ligand ICOSL (B7RP-1, B7H-2) have been shown to affect T-cell responses via ICOS-mediated PI3-kinase signaling to enhance the T-cells’ development and activity. In addition, previous studies have shown that ICOS/ICOSL pathway may play an important role in CTLA4 inhibitor-induced tumor immunity. In this study, we aim to develop and implement the Fc-fusion recombinant ICOSL proteins to induce T-cells’ activation for therapeutic use. Our data suggested that recombinant ICOSL-Fc can enhance the proliferation and cytotoxicity effect of human T-cells by increasing INF-γ and IL10 secretion. Moreover, ICOSL-Fc can also inhibit tumor growth in xenograft animal models. Based on our study, ICOS/ICOSL pathway could be a promising therapeutic target for the immunotherapy.

Citation Format: Yu-Hsun Lo, Cheng-Chou Yu, Shu-Han Yu, Tsung-Hang Hseih, Mei-Chi Chan, Tsai Shih-Chong. Targeting ICOS receptor for development of cancer immunotherapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A200.