Results from the first clinical trial of a new personalized cancer vaccine for advanced melanoma were presented at the American Association for Cancer Research (AACR) Annual Meeting in Atlanta, Georgia, in March 2019.
NEO-PV-01, an investigational agent being developed by Neon Therapeutics, is a bespoke cancer vaccine being designed to generate immune responses against specific neoantigens found in an individual’s tumor. Neoantigens, formed from DNA mutations in cancer cells, are important targets for T-cell mediated antitumor responses.
NEO-PV-01 contains up to 20 neoantigen peptides personally selected for each patient by analysis of the tumor and a bioinformatics pipeline called RECON. The aim is that the cancer vaccine can boost T-cell responses to these tumor-specific neoantigen peptides and unleash the immune system.
The treatment is currently being tested in trials for metastatic melanoma, bladder cancer, and non-small cell lung cancer (NSCLC). Results were the most advanced in melanoma, and therefore, were featured in the AACR presentation.
“All 3 cohorts – melanoma, NSCLC, bladder – these are very high-mutational-load cancers and the chances of finding high-quality epitopes or high-quality neoantigens that we can make vaccines for is higher here,” explained Lakshmi Srinivasan, PhD, director of immune monitoring at Neon Therapeutics and presenter of the work at AACR.
To make the neoantigen treatment, samples from the tumor are sent for DNA sequencing and RNA profiling, in addition to analysis of the patient’s MHC class 1 antigen presentation machinery, which displays any neoantigens for recognition by T cells. All of these data are input into RECON, which calculates which of the 20 neoantigens are most likely to stimulate the immune response and which should be in the personalized cancer vaccine.