Personalized neoantigen cancer vaccines: current progression, challenges and a bright future

Tumor neoantigens possess specific immunogenicity and personalized therapeutic vaccines based on neoantigens which have shown promising results in some clinical trials, with broad application prospects. However, the field is developing rapidly and there are currently few relevant review articles. Summarizing and analyzing the status of global personalized neoantigen vaccine clinical trials will provide important data for all stakeholders in drug development. Based on the Trialtrove database, a retrospective analysis was conducted using trial quantity as a key indicator for neo-adjuvant and adjuvant therapy anti-PD-1/PD-L1 clinical trials initiated before the end of 2022. The time trend of newly initiated trials was investigated. The sponsor type, host country, treatment mode, combination strategy, tested drugs, and targeted cancer types of these trials were summarized. As of December 2022, a total of 199 trials were included in the analysis. Among these studies, Phase I studies were the most numerous (119, 59.8%), and Phase I studies have been the predominant study type since 2015. Peptide vaccines were the largest neoantigen vaccines type, accounting for 64.8% of all clinical trials. Based on peptide delivery platforms, the proportion of trials was highest for the DC system (32, 16.1%), followed by LNP (11, 5.5%), LPX (11, 5.5%), and viruses (7, 3.5%). Most vaccines were applied in trials as a monotherapy (133/199, 66.8%), meanwhile combining immunotherapeutic drugs was the most common form for combination therapy. In terms of indications, the largest number of trials involved three or more unspecified solid tumors (50/199, 25.1%), followed by non-small cell lung cancer (24/199, 12.1%) and pancreatic cancer (15/199, 7.5%). The clinical development of personalized neoantigen cancer vaccines is still in the early stage. A clear shift in delivery systems from peptides to DC and liposomal platforms, with the largest number of studies in Asia, collectively marks a new era in the field. The adjuvant or maintenance therapy, and the combination treatment with ICIs are becoming the important clinical development orientation. As research on tumor-immune interactions intensifies, the design, development, and application of neoantigen vaccines are bound to develop rapidly, which will bring a new revolution in the future cancer treatment.