Allogeneic Tumor Antigen-Specific T Cells for Broadly Applicable Adoptive Cell Therapy of Cancer.

Abstract

T cells specific for major histocompatibility complex (MHC)-presented tumor antigens are capable of inducing durable remissions when adoptively transferred to patients with refractory cancers presenting such antigens. When such T cells are derived from healthy donors, they can be banked for off-the-shelf administration in appropriately tissue matched patients. Therefore, tumor antigen-specific, donor-derived T cells are expected to be a mainstay in the cancer immunotherapy armamentarium. In this chapter, we analyze clinical evidence that tumor antigen-specific donor-derived T cells can induce tumor regressions when administered to appropriately matched patients whose tumors are refractory to standard therapy. We also delineate the landscape of MHC-presented and unconventional tumor antigens recognized by T cells in healthy individuals that have been targeted for adoptive T cell therapy, as well as emerging antigens for which mounting evidence suggests their utility as targets for adoptive T cell therapy. We discuss the growing technological advancements that have facilitated sequence identification of such antigens and their cognate T cells, and applicability of such technologies in the pre-clinical and clinical settings.