Targeted expansion of cytotoxic T cells using IL-12 and CD137L supplementation enhances antitumor efficacy

The increasing success of allogenic Vδ2 T cell immunotherapy for the treatment of cancer has been demonstrated in recent studies. Vδ2 T cells recognize phosphoantigens, intermediates of the mevalonate pathway, through butyrophilin molecules, and they are not major histocompatibility complex (MHC) restricted. Allogeneic transfer of <i>in vitro</i> expanded Vδ2 T cells has shown more promising results than autologous strategies, although the clinical benefit remains limited. One of the issues leading to less-than-optimal responses relates to the polyclonal expansion of Vδ2 T cell subsets with variable cytotoxic capacity. Previous work developed protocols to expand Vδ2 T cells, although to our knowledge, ours is the first comprehensive study that has produced a simple, antigen-presenting feeder-free culture that produced an average expansion of 3,000-fold and more than 95% pure Vδ2 T cells avoiding additional isolation steps. Here, we show the <i>in vitro</i> expansion of cytotoxic Vδ2 T cells expressing CD16 and NKG2A enriched in granzyme B that displayed enhanced antitumor activity of up to 40% against leukemia and ovarian, breast, and lung cancer cells. Our work warrants clinical testing to evaluate the therapeutic potential of these highly cytotoxic cells, paving the way for improved efficacy of personalized cell-based immunotherapies.