The team behind Project A08 focuses on IL-10-mediated immunosuppression as a critical barrier limiting the functionality of donor-derived CAR T memory stem cells (TSCM) in B-cell malignancies relapsing after ASCT. On the basis of their successful first-in-human clinical use of engineered TSCM cells, they are now advancing their GvL potency by equipping them with novel synthetic receptors designed to sustain stemness. Furthermore, based on our newly developed semi-automated manufacturing process, our future studies will aim to translate an improved bispecific CAR TSCM platform into clinical testing.

Professor Luca Gattinoni has been dedicated to developing curative T-cell-based immunotherapies in advanced cancer patients for over 20 years. Throughout his career a central theme of his research has been to elucidate how the differentiation state of T cells impacts their effectiveness in adoptive T-cell transfer for tumor eradication. His discoveries have fundamentally shaped the current view in the field which now recognizes the superior therapeutic potential of early memory T cells compared to cytotoxic effector T cells (Gattinoni L. et al, J Clin Invest, 2005 and Gattinoni L. et al, Nat Med, 2009).

Within this framework, Professor Gattinoni uncovered a unique subset of minimally differentiated memory T cells characterized by stem cell-like attributes, aptly named stem cell memory T cells (Tscm). And provided the first evidence that these cells mediate superior antitumor responses after adoptive transfer (Gattinoni L, et al. Nat. Med, 2011).