Adoptive Cellular Therapies for Cancer, Autoimmunity and Transplant

The use of cellular therapies that modulate the immune system for therapeutic gain in cancer, autoimmunity and transplant has garnered significant attention over the last decade. Different immune cell subsets have been adoptively transferred, with T and NK cells for cancer immunotherapy being the most investigated. The remarkable success of genetically redirected CD19-targeted chimeric antigen receptor T cells (CART-19) in patients with B cell malignancies has permanently changed human cancer therapy. CART-19 was the first engineered cellular therapy to receive FDA approval and paved the way for increasingly complex engineering strategies to increase CAR-T efficacy and enable the use of allogeneic CAR-T cells in unmatched hosts. T cells have also been engineered with chimeric autoantigen receptors (CAAR-T) that consist of a known autoantigen linked to T cell intracellular signaling domains. CAART cells specifically deplete autoreactive B cells which has the potential to cure autoimmune disease without global immune suppression. Additional cellular strategies are being explored that leverage the natural properties of rare immune cell subsets such as iNKT cells, that due to their invariant T cell receptor can be adoptively transferred into an unrelated host, without GVHD and can orchestrate an immune suppressive milieu that promotes allo-iNKT engraftment without compromising potent cytotoxic function. These cells are currently being explored as CAR-iNKT for cancer and as a tolerizing strategy for successful transplant. These cellular therapies are all currently under investigation in the canine clinics and the progress of these efforts in dogs will be discussed in this lecture.