09:00 AM - 11:00 AM CET
17:00 PM - 19:00 PM JST
Yuki Kagoya, M.D., Ph.D.
Aichi Cancer Center Research Institute
Genetic modification of antitumor T cells for optimal adoptive cancer immunotherapy
Adoptive immunotherapy, in which antitumor T cells are prepared in vitro and infused back into the patient, is a potentially curative approach for patients with relapsed or refractory cancer as exemplified by recent success in chimeric antigen receptor (CAR)-engineered T cell therapy against B-cell malignancies. Further improvement is required to enhance the efficacy as well as versatility of this therapy. In this webinar, I will discuss the molecular attributes of T cells essential for durable therapeutic response and how to reprogram dysfunctional T cells to acquire superior antitumor functions.
Sebastian Amigorena, Ph.D.
Institut Curie, Paris
Epigenetic re-programing of CAR-T cells Suv39h1 ablation
CAR-T cell theraies are very efficient in heme malignancies, but not in solid tumors. We showed previously that genetic ablation or pharmacological inhibition of the H3K9- histone methyltransferase Suv39h1 delays tumor growth and potentiates tumor rejection by anti-PD-1 in mouse pre-clinical models. In the absence of Suv39h1, anti-PD-1 favors chromatin opening in loci linked to T-cell activation, memory pluripotency, but in the absence of Suv39h1, cells acquire accessibility in cytolytic effector loci. Targeting of Suv39h1 in human CAR-T enhances the rejection of established solid tumors in humanized mice and augments strongly CAR-T survival in vivo, allowing long-term protection against tumor re-challenges. Overall, Suv39h1 inhibition enhances immunotherapy by anti-PD-1 and CAR-T.