Synthetic Peptide Vaccine Platforms Targeting Tumor-Specific Antigens: Advances and Challenges

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Background

It has long been known that tumor-specific antigens (TSAs) that are preferentially expressed on various cancer cells are potentially interesting targets for CD8+ class I epitope targeting. First, unlike neoantigens which result from small changes in expressed DNA, TSAs are generally more immunogenic because they are coded by parts of the exome that are not normally expressed and therefore are seen as more “foreign” by the immune system. Second, because TSAs by definition have very low expression rates on normal tissue, the risk of “off-targeting” by a T-cell attack on normal cells is mitigated.

There are many approved products based on cytotoxic T lymphocytes (CTL) targeting of tumors. These are currently limited to checkpoint inhibitors, that can cause non-specific CTL attacks. Techniques that produce tumor-specific killer T-cell populations using autologous T-cells modified in-vitro (CAR-T) or by incubating autologous T-cells with tumor cells and subsequently re-infusing these T-cells into the patient are also currently used. These approaches require complex manufacturing processes using cell culture and have been associated with significant side effects such as cytokine storm seen with CAR-T therapy. All of the approved products in this space are expensive, potentially further contributing to social inequities in healthcare.

Pre-clinical and clinical studies using a variety of techniques to elicit a CD8+ attack against TSAs such as sequences on HER2 and Survivin (BRIC5) have been reported. Approaches used by investigators to create CTL attacks on TSA class I peptide sequences have ranged from “neat peptides” delivered in combination with various adjuvants including granulocyte stimulating factor and interferons, to “beads on a string” approaches designed to elicit T-cell expansion against tumor antigen targets. Results of these studies have been mixed; lack of a consistent, robust T-cell expansion against the target peptides and not using optimal peptides for CTL attack, may result in these results.

This Research Topic will focus on new tools to predict and evaluate CTL response to TSAs. This will include analysis of synthetic vaccine platforms capable of producing robust CTL expansion against specific class I peptides on TSAs and data showing efficacy using in-vitro tumor cell culture experiments and animal models. We welcome published databases listing class I peptide targeting by cancer patients that could be used to develop and validate TSA CTL targeting tools.

With this Research Topic, we welcome the submission of Original Research, Brief Research Report, Data Report, Technology and Code article types focusing on the use of novel synthetic peptide vaccine platforms that show efficacy against CTL targets on TSAs using in-vitro cell-kill tissue culture experiments or in-vivo using appropriate animal tumor models. The following themes, including but not limited to those in the list below can be included:

- Demonstrating efficacy of specific class I CTL targets on TSAs in cell culture with human tumor cell targeting
- Demonstrating efficacy of specific class I CTL targets on TSAs in cell culture with animal models
- Novel in-vitro / preclinical models for CTL targeting of TSAs
- T-cell response databases of cancer patients cataloging class I targets on TSAs
- Novel computational models predicting optimal targets for CTL attack against TSAs
- Novel synthetic peptide vaccine platforms with demonstrated ability to mount CTL expansion against TSAs.

Please note: Original research based solely on in silico techniques will not be considered for review.

Note on editors: Topic editor Dr. Reid Rubsamen is employed by Flow Pharma, Inc. and Topic Editor Dr. Andrew Sloan works on grant applications with Merck and NIH.

Keywords: Cytotoxic T Lymphocyte, CTL, Tumor Specific Antigen, TSA, peptide vaccine, synthetic vaccine, immunotherapy

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