CIBSS - Centre for integrative Biological Signalling StudiesCIBSS

CIBSS-C

Aligning dynamic TCR assembly with optimal anti-tumour responses

PD Dr. Susana Minguet (CIBSS-AI), Institute of Biology III – Immunology (Faculty of Biology), University of Freiburg

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Cancer immunotherapy is a major breakthrough in the treatment against cancer. Several proof-of-principle studies have demonstrated the enormous potential of engineering chimeric antigen receptor (CAR)-expressing T cells for the adoptive therapy of select cancers. However, important bottlenecks in such therapies are T cell exhaustion by inhibitory receptors or by metabolic programs incompatible with T cell activation and tumour antigen escape. We have engineered and mechanistically characterized chimeric TCRs, consisting of an scFv fragment fused to a fully functional TCR (scTCR, (Minguet et al., 2007)). We aim here to investigate whether scTCRs expressing an anti-tumour scFv are more potent in eradicating solid human tumours in mouse models than CARs expressing the same scFv. Our goal is to best aligning receptor design with optimal anti-tumour responses. We will test these new CIBSS-scTCRs for metabolic reprograming, signal transduction, cell fate decisions and ultimate, anti-tumour efficacy in humanized tumour models together with R. Zeiser, O. Gross and E. Pearce.