Vγ9Vδ2TCR and Beyond: Novel Insights and Strategies for Advanced T cell-based Immunotherapies

Abstract

Immunotherapy in general and CAR-T cell therapy in particular have emerged as groundbreaking approaches in the way we treat cancer by harnessing the power of the human immune system during the past decades. Despite their high success rates in some tumor types, many patients, especially those with solid tumors, still fail to benefit from this treatment. In this thesis we aim to improve engineered T cell therapies, with a focus on T cells engineered to express a defined γδ TCR (TEGs), by tackling from various sites: First, improving pre-treatment patient screening for Vγ9Vδ2TCR-based therapies by providing new insights into the recognition mechanism of those special TCRs. Second, by identifying and analyzing the most potent subsets of engineered T cells, and finally by modifying T cells for improved migration to the tumor site, tumor infiltration of the immunosuppressive tumor microenvironment and tumor killing.