Abstract
One of the principal goals of cancer immunotherapy is the development of efficient therapeutic cancer vaccines that are able to elicit an effector as well as memory T cell response specific to tumor antigens. In recent years, the attention has been focused on the personalization of cancer vaccines. However, the efficacy of therapeutic cancer vaccines is still disappointing despite the large number of vaccine strategies targeting different tumors that have been evaluated in recent years. While the preclinical data have frequently shown encouraging results, clinical trials have not provided satisfactory data to date. The main reason for such failures is the complexity of identifying specific target tumor antigens that should be unique or overexpressed only by the tumor cells compared to normal cells. Most of the tumor antigens included in cancer vaccines are non-mutated overexpressed self-antigens, eliciting mainly T cells with low-affinity T cell receptors (TCR) unable to mediate an effective anti-tumor response. In this review, the target tumor antigens employed in recent years in the development of therapeutic cancer vaccine strategies are described, along with potential new classes of tumor antigens such as the human endogenous retroviral elements (HERVs), unconventional antigens, and/or heteroclitic peptides.
Highlights
Preventive vaccines were originally developed to elicit an antigen-specific memory immunity in healthy subjects that is able to promptly react to subsequent infections by pathogens that could occur during the lifetime
The only FDA-approved therapeutic cancer vaccine to date is Provenge® for patients with castration-resistant prostate cancer, which showed a limited 4.5-month improvement in overall survival (OS) compared to the placebo [5,6]. Such limited efficacy may be ascribed to two main factors: the immunosuppressive factors infiltrating the tumor microenvironment (TME) and the specificity of target tumor antigens included in the vaccine formulation
We showed that neither the Tumor Mutational Burden (TMB) nor the number or the quality of the predicted neoantigens are associated with a prolonged survival in Hepatocellular carcinoma (HCC) patients not undergoing immunotherapy treatment
Summary
Preventive vaccines were originally developed to elicit an antigen-specific memory immunity in healthy subjects that is able to promptly react to subsequent infections by pathogens that could occur during the lifetime. In addition to a memory immunity, such vaccines are intended to elicit a potent anti-cancer effector immune response This mechanism involves the professional antigen-presenting cells (APCs) for triggering a cytotoxic effector CD8+ T-cell (CTL) response. The only FDA-approved therapeutic cancer vaccine to date is Provenge® for patients with castration-resistant prostate cancer, which showed a limited 4.5-month improvement in overall survival (OS) compared to the placebo [5,6]. Such limited efficacy may be ascribed to two main factors: the immunosuppressive factors infiltrating the tumor microenvironment (TME) and the specificity of target tumor antigens included in the vaccine formulation. Target tumor antigens employed in recent years in the development of therapeutic cancer vaccine strategies are described, together with potential new classes of tumor antigens, such as the human endogenous retroviral elements (HERVs), as unconventional antigens and/or heteroclitic peptides
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