Cytokine Pre-activated γδT cells in Cancer Adoptive Immunotherapy

Abstract

Abstract Adoptive cell therapy harnesses the power of immune system by stimulating and expanding immune cells to combat cancer. The application of tumour-specific αβT cell-based therapy may be hindered by limited tumour antigens. γδT cells are promising candidates for cellular immunotherapy because of their abundant IFN-γ or IL-17 production and MHC-independent cytotoxicity against a broad spectrum of tumors. Numerous attempts to use γδT cells in cancer immunotherapy have been made and resulted in variable efficacy and an overall good safety profile. Better expansion strategies are needed to improve the efficacy of the clinical trials using γδT cell-based immunotherapies. In the current project, we aim to explore the efficacy of cytokine pre-activated γδT cells in cancer immunotherapy. Pre-activated γδT cells by a combination of cytokines were characterised for their surface activation marker expression, cytokine production, and cytotoxicity against tumour cells. We found that IL-12/18, IL-12/15/18, IL-12/18/21 and IL-12/15/18/21 are the most effective cytokine combinations for in vitro expansion of γδT cells in terms of activation and cytokine production. IL-21 upregulated their cytotoxicity against tumour cells in murine systems. All four combinations showed upregulated cytotoxicity of human γδT cells. These findings were extended to in vivo studies using murine hepatocellular carcinoma model.