Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy

Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (T SCM ) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8 + T SCM cells can be generated in vitro from naive CD8 + T cells via Wnt signalling; however, methods do not yet exist for inducing T SCM cells from activated or memory T cells. Here, we show a strategy for generating T SCM -like cells in vitro (iT SCM cells) from activated CD4 + and CD8 + T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iT SCM cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy. Tumour-specific T cells can be expanded in vitro and adoptively transferred for therapy, but this strategy is limited by induction of short-lived T cell populations. Here the authors activate Notch signalling in cultured mouse or human T cells, resulting in the production of a long-lived stem cell memory T cell population that can fight tumours in mice.