Researchers Examine Potential of Personalized Neoantigen-Based Vaccines for Cancer

As researchers continue to determine approaches for improving the number of patients who can benefit from immune checkpoint inhibitor (ICI) therapy, a group of investigators highlighted the potential of neoantigens as possible treatment targets.

In their paper, which reviews the evidence and technologies for neoantigen-based personalized vaccines, the researchers explained that neoantigens are important targets of T cell-mediated anti-tumor immunity. In addition, advances like next-generation sequencing have identified several genetic biomarkers—such as mismatch DNA repair—that measure high neoantigen load, they noted.

“Recent success of ICIs in tumors with high tumor mutational burden (TMB), which is a measurement of cancer neoantigens and tumor antigenicity, supports the current development of neoantigen-based personalized cancer vaccines for patients with high TMB tumor,” explained the researchers. “Several studies have shown neoantigen vaccines are feasible, safe and have promising clinical activity in patients with high TMB tumors in both metastatic and adjuvant settings.”

According to the authors, there are various clinical trials assessing the potential of neoantigen-based cancer vaccines, including the NEO-PV-01 trial—an open-label, phase 1b trial of the NEO-PV-01 vaccine in combination with nivolumab in 82 patients with advanced melanoma. Throughout the study, as many as 20 unique peptides are collected from a patient’s tumor for manufacture. Data showed that the treatment combination prompted durable neoantigen-specific T cell reactivity that proved cytotoxic to tumors. The combination was also safe, with no reported treatment-related serious adverse events.

A small study of 8 patients with surgically resected stage 3b/c or IVM1a/b melanoma showed that personalized neoantigen peptide vaccines produced long-term T cell responses and widened the spectrum of tumor-specific cytotoxicity, indicating the vaccines induced persistent memory T cells and epitope spreading. At a median 4 years of follow-up, all patients were alive and 6 exhibited no evidence of active disease.

“These data support the feasibility, safety, antigen-specific immunity, and promising early and long-term antitumor activity of this personalized neoantigen-based therapeutic strategy in patients with advanced solid tumors in both metastatic and adjuvant settings,” commented the researchers, adding that to date, the majority of these trials have tested peptide delivery platforms.

In some trials, messenger (m)RNA vaccines have been assessed and have also yielded promising results, researchers said. They noted that the emergence of mRNA-based vaccines for COVID-19 has brought more attention to using the vaccine in cancer.

In a phase 1 study of the mRNA-4157 vaccine in combination with pembrolizumab in patients with Human Papillomavirus-negative head and neck squamous cell carcinoma, participants demonstrated an overall response rate (ORR) of 50% after receiving the combination, compared with an ORR rate of 14.6% among patients who received pembrolizumab alone. Median progression-free survival was 9.8 months among patients receiving the combination compared with 2 months among patients receiving just pembrolizumab.

Reference:

Ma W, Pham B, and Li T. Cancer neoantigens as potential targets for immunotherapy. Clin Exp Metastasis. Published online May 5, 2021. doi:10.1007/s10585-021-10091-1