Figure 1. TCRs that recognize tumor antigen epitopes that encompass oncoprotein mutations have potential for potent immunotherapy.

For many types of cancer, small molecule inhibitors to specific oncoproteins have not been identified or have limited efficacy due to off-target effects and acquisition of treatment resistance. In this issue, Veatch and colleagues characterized the T cell response in a patient who had a complete tumor response following infusion of tumor-infiltrating T cells that targeted multiple tumor antigens. TCRs from this patient recognized an epitope that encompassed the driver mutation within an oncoprotein. Targeting of oncoproteins with T cells, which kill tumor cells, rather than small molecules, which inhibit tumor cells, may permit the development of more effective treatments. Additionally, the highly specific oncoprotein targeting by TCRs may reduce the off-target toxicity of treatment.