Neoantigen Vaccines; Clinical Trials, Classes, Indications, Adjuvants and Combinatorial Treatments

SIMPLE SUMMARY: Personalized neoantigen vaccines are a diverse group of personally tailored cancer vaccines that strengthen patients´ own immune reaction against cancer antigens. We analyzed 147 neoantigen vaccine clinical trials from ClinicalTrials.gov database and showed that peptide vaccines were the dominating vaccine type, while there were multiple new neoantigen vaccine types in the field. We also showed that neoantigen vaccines were mostly used in the treatment of small cell lung cancer, non-small cell lung cancer, melanoma, and glioma. According to our results neoantigen vaccines work at their best when combined with other treatments such as immune checkpoint inhibitors, chemotherapy, and radiation therapy. The effect of some neoantigen vaccine types were also often promoted with adjuvant therapy where poly-ICLC were the most recurrent adjuvant choice. ABSTRACT: Personalized neoantigen vaccines are a highly specific cancer treatment designed to induce a robust cytotoxic T-cell attack against a patient’s cancer antigens. In this study, we searched ClinicalTrials.gov for neoantigen vaccine clinical trials and systematically analyzed them, a total of 147 trials. Peptide vaccines are the largest neoantigen vaccine type, comprising up to 41% of the clinical trials. However, mRNA vaccines are a growing neoantigen vaccine group, especially in the most recent clinical trials. The most common cancer types in the clinical trials are glioma, lung cancer, and malignant melanoma, being seen in more than half of the clinical trials. Small-cell lung cancer and non-small-cell lung cancer are the largest individual cancer types. According to the results from the clinical trials, neoantigen vaccines work best when combined with other cancer treatments, and popular combination treatments include immune checkpoint inhibitors, chemotherapy, and radiation therapy. Additionally, half of the clinical trials combined neoantigen vaccines with an adjuvant to boost the immune effects, with poly-ICLC being the most recurrent adjuvant choice. This study clarifies the rapid clinical trial development of personalized neoantigen vaccines as an emerging class of cancer treatment with increasingly diversified opportunities in classes, indications, and combinatorial treatments.