Postdoctoral Fellow

Job DescriptionAdoptive cell therapy demonstrates remarkable success in in the treatment of malignancies. This therapy relies on the infusion of tumor-specific T cells that subsequently trace and kill tumor cells. Besides non-modified T cells, such as tumor-infiltrating lymphocytes (TILs), T cells are often derived from blood and redirected toward cancer antigens via gene-engineering with chimeric antigen receptors (CARs) or T cell receptors (TCRs). CAR-T cell therapy has elicited profound responses in hematological malignancies, whereas TIL and TCR-T cell treatments have shown responses in solid tumors, such as melanoma and synovial sarcoma. Despite this tremendous progress, there is still an urgent need to identify and exploit new, tumor-specific targets.Many tumors escape treatments, such as checkpoint inhibitors, by an adaptive feedback response that activates immunosuppressive pathways. For example, T cells that are initially activated often mediate the induction of immune suppressive enzymes, such as indoleamine 2,3-dioxygenase 1 (IDO1). The creation of novel and unique epitopes, as a consequence of above adaptive response, diversifies the landscape of the cancer’s immunopeptidome and discloses potentially new targets for TCR-T therapy.In this project, where Erasmus MC works together with NKI, this new class of epitopes will be used to generate and select TCR-T cells as a prelude to their potential clinical utilization. You will make use of multiple state-of-the-art technologies to identify and validate epitopes as well as TCRs, ranging from in silico and molecular tools to in vitro assays with tumor organoids and in vivo experiments.The candidate researcher will work closely with experienced technicians, PhD students and is involved in the writing of scientific publications and grant applications.