Engineering the next-generation of T cell-based cancer immunotherapies

Abstract

Due to their intrinsic characteristics, T cells are currently being explored in the immunotherapy field as new therapeutic agent against cancer. In this thesis we provide insights for the development and improvement of the next generation of γδTCR and αβTCR based therapies. First, we developed a new concept by generating γδTCR based bispecifics that were able to redirect αβT-cells towards a broad panel of hematological and solid tumors. Second, we improved the potency of two previously described αβT-cells engineered to express a γδTCR (TEG011 and TEG001) by introducing natural or chimeric co-receptors and improving performance of CD4 and/or CD8s. Last, we described a novel method to increase purity of engineered T-cells by murinization of the introduced αβTCR.