Abstract
The success of the immune checkpoint blockade has provided a proof of concept that immune cells are capable of attacking tumors in the clinic. However, clinical benefit is only observed in less than 20% of the patients due to the non-specific activation of immune cells by the immune checkpoint blockade. Developing tumor-specific immune responses is a challenging task that can be achieved by targeting tumor antigens to generate tumor-specific T-cell responses. The recent advancements in peptide-based immunotherapy have encouraged clinicians and patients who are struggling with cancer that is otherwise non-treatable with current therapeutics. By selecting appropriate epitopes from tumor antigens with suitable adjuvants, peptides can elicit robust antitumor responses in both mice and humans. Although recent experimental data and clinical trials suggest the potency of tumor reduction by peptide-based vaccines, earlier clinical trials based on the inadequate hypothesis have misled that peptide vaccines are not efficient in eliminating tumor cells. In this review, we highlighted the recent evidence that supports the rationale of peptide-based antitumor vaccines. We also discussed the strategies to select the optimal epitope for vaccines and the mechanism of how adjuvants increase the efficacy of this promising approach to treat cancer.
Highlights
The recent in-depth understanding of basic immunology has resulted in the translation of cancer immunotherapy from the bench to clinical practice
Since Immune checkpoint inhibitors (ICIs) are considered as the fourth step in cancer therapy after surgery, radiation, and chemotherapy, the responders to ICIs are limited to approximately 20% [1]
Incomplete Freund’s adjuvant (IFA) has often been used as an adjuvant for various cancer vaccine clinical trials, the objective response is less than 3% [63]
Summary
The recent in-depth understanding of basic immunology has resulted in the translation of cancer immunotherapy from the bench to clinical practice. A limitation of this treatment is that ICIs alone cannot selectively activate cancer-specific T-cells. T-cells, usually have low-affinity TCRs, the selective activation of these cells is necessary to achieve antitumor activity by overwhelming irrelevant T-cells for antigen-presenting cells (APCs) and cytokine competition [2]. Epitopes from intracellular antigens are presented on MHC class I through the proteasome in APCs (or tumor) to stimulate CD8 T-cells (CTLs). Unlike MHC class I, the epitope peptide presented on MHC class II is processed from extracellular antigens through endosomes to stimulate CD4 T-cells (HTLs). The peptide vaccines have advantages over other tumor immunotherapies because of their tumor-specificity, simplicity, and cost-effectiveness; there is still room for the improvement in the application of this therapy as a standard option in cancer therapy. We will discuss the strategies to select appropriate peptides and immune adjuvants for antitumor immunity and the current progress in peptide-based tumor immunotherapy
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