Abstract
Many immunotherapies rely on CD8+ effector T cells to recognize and kill cognate tumor cells. These T cell-based immunotherapies include adoptive cell therapy, such as CAR T cells or transgenic TCR T cells, and anti-cancer vaccines which expand endogenous T cell populations. Tumor mutation burden and the choice of antigen are among the most important aspects of T cell-based immunotherapies. Here, we highlight various classes of cancer antigens, including self, neojunction-derived, human endogenous retrovirus (HERV)-derived, and somatic nucleotide variant (SNV)-derived antigens, and consider their utility in T cell-based immunotherapies. We further discuss the respective anti-tumor/anti-self-properties that influence both the degree of immunotolerance and potential off-target effects associated with each antigen class.
Highlights
The current pillars of cancer treatment include surgery, chemotherapy, radiation therapy, targeted therapy, and more recently, immunotherapy
This review will discuss the various types of cancer antigens, focusing on antigens from neojunctions and retroelements in the genome, and the implications they have on the outcome of T cell-based immunotherapy
As T cells develop in the thymus, they undergo positive and negative selections that center on the strength of the interaction between the thymocytes’ T cell receptor (TCR)
Summary
The current pillars of cancer treatment include surgery, chemotherapy, radiation therapy, targeted therapy, and more recently, immunotherapy. The emergence of immunotherapy as a fifth pillar in cancer treatment is the result of research spanning decades that have advanced our understanding of T cell-mediated immunity, some of which will be touched upon in this review. The T cell-mediated immunotherapies used today include adoptive cell therapy (ACT), anti-cancer vaccines, and immune checkpoint inhibitor (ICI) therapy. Paramount to both the efficacy and potential toxicity of T cell-based immunotherapies are the antigens they target. This review will discuss the various types of cancer antigens, focusing on antigens from neojunctions and retroelements in the genome, and the implications they have on the outcome of T cell-based immunotherapy
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