The Pluripotent Path to Immunotherapy

Adoptive cell therapy (ACT) enhances the patient's own immune cells' ability to identify and eliminate cancer cells. Several immune cell types are currently being applied in autologous ACT, including T cells, natural killer (NK) cells and macrophages. The cells' inherent anti-tumor capacity can be used, or they can be targeted towards tumor associated antigen through expression of a chimeric antigen receptor (CAR). Although CAR-based ACT has achieved great results in hematological malignancies, the accessibility of ACT is limited by the autologous nature of the therapy. Induced pluripotent stem cells (iPSCs) hold the potential to address this challenge, as they can provide an unlimited source for the in vitro generation of immune cells. Various immune subsets have been generated from iPSC for the application in ACT, including several T cell subsets (αβT cells, mucosal-associated invariant T cells, invariant NKT (iNKT) cells and γδT cells), as well as NK cells, macrophages and neutrophils. iPSC-derived αβT, NK and iNKT cells are currently being tested in Phase-I clinical trials. The ability to perform (multiplexed) gene editing at the iPSC level and subsequent differentiation into effector population not only expands the arsenal of ACT but allows for development of ACT utilizing cell types which cannot be efficiently obtained from peripheral blood or engineered and expanded in vitro.