Method to direct T-cell fate towards T stem cell memory phenotype

Researchers at Stanford have developed a method to direct T cell fate toward the T stem cell memory (TSCM) phenotype during ex vivo expansion for adoptive cell transfer (ACT) therapies. During ACT, tumor-specific lymphocytes are expanded ex vivo and then administered to the patient as a therapeutic to treat cancer. Sometime these T cells are also engineered with chimeric antigen receptors (CAR) that enable these cells to specifically recognize and kill cancer cells. TSCM cells are a subset of memory lymphocytes that have a stem cell-like ability to self-renew and the multipotent capacity to differentiate into memory and effector T cell subsets. Increasing the numbers of TSCM cells has been suggested as a way to improve the efficacy of ACT therapies. Current approaches to do so, however, are limited as TSCM cells constitute a very rare subset of T cells that are hard to obtain and culture. Thus, new methods are needed to enhance the TSCM population. To help meet this need, the inventors have developed a method that uses drugs to disrupt specific signaling pathways during T cell activation to skew T cell differentiation to the TSCM phenotype. This technology provides a simple non-genetic method for the expansion of T cells ex vivo in a manner that greatly enhances the number of TSCM cells. It has the potential to improve clinical outcomes for cancer immunotherapy patients.

Stage of research
Preliminary data shows that culturing CAR-T cells in the presence of ibrutinib can endow a more TSCM phenotype, reduce expression of inhibitory receptors, and enhance functionality.