On Thursday (29.01) we will host Prof. Dinorah Friedmann-Morvinski (Cancer Biology Research Center, Tel Aviv University). Her lecture will be entitled: "NOVEL STRATEGIES TO ENHANCE THE EFFICACY OF CAR T CELL IMMUNOTHERAPY IN BRAIN TUMORS". The lecture will take place at 3 p.m. in the CN lecture hall and it will be followed by a get together.

Abstract:

Conventional therapies have not led to significant improvements in the survival outcomes of patients with glioblastoma (GBM), prompting increasing efforts to develop new therapeutic strategies, particularly in the expanding field of chimeric antigen receptor (CAR) T-cell immunotherapy. However, CAR T-cell therapy in GBM, and in solid tumors in general, faces several challenges, including tumor heterogeneity and a hostile tumor microenvironment (TME).

We recently reported the design of a CAR targeting a novel tumor-associated antigen in GBM. The engineered CAR T cells not only recognize and kill tumor cells but also tumor-derived endothelial cells. We showed that treatment with these specific CAR T cells reduced blood vessel density and significantly prolonged survival in preclinical GBM models.

To overcome some of the barriers presented by the hostile TME, we are exploring strategies to boost CAR T-cell efficacy and persistence. This includes pairing them with immunomodulatory agents that can reverse the immunosuppressive environment and enhance T-cell mechanisms. We are also improving CAR T-cell metabolic fitness to cope with nutrient-deprived TMEs, particularly glucose scarcity. Our engineered "metabolically superior" cells utilize alternative energy sources, enabling them to thrive in unfavorable conditions. These cells show enhanced survival, proliferation, and cytokine secretion, indicative of sustained effector functions crucial for antitumor immunity. Preliminary in vivo results reveal significantly improved efficacy of metabolically superior CAR T-cell therapy in preclinical GBM models.

While GBM poses challenges for CAR T-cell therapy, combining CAR T cells with enhanced metabolic capabilities and nanomedicines designed to remodel the TME offers a promising therapeutic approach.