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Small Study Confirms Feasibility of a Personalized Neoantigen Vaccine for Melanoma

Surabhi Dangi-Garimella, PhD
A new study, published in the journal Nature, has confirmed the efficacy of a melanoma vaccine targeted against 20 predicted personal tumor neoantigens in 6 patients.
A new study, published in the journal Nature, has confirmed the efficacy of a melanoma vaccine targeted against 20 predicted personal tumor neoantigens in 6 patients, 4 of whom had no recurrence at 2 years. The 2 patients who had recurrence responded well to subsequent treatment with an immune checkpoint inhibitor drug.

This phase 1 study was conducted in treatment-naïve patients with high-risk melanoma (stage IIIB/C and stage IVM1a/b) who had undergone surgical resection. Initially, 10 patients were enrolled, 8 of whom had an expected high tumor mutation rate, with mutations in BRAF and NRAS among others. Following whole-genome sequencing of matched tumor and normal cell DNA from each patient and predicting which mutated peptides would bind autologous human leukocyte antigen (HLA)-A or B proteins in the patient, clinical-grade immunizing long peptides were generated (15 to 30 amino acids in length; 13 to 20 peptides per patient). Six patients participated in the vaccination at a minimum of 18-weeks post surgery, and were administered 5 priming and 2 booster vaccines.

The authors hypothesized that vaccination with neoantigens could expand the existing neoantigen-specific T-cell population and induce a broader population of new T-cell specificities in the vaccinated patients, ultimately improving the cancer control capacity of the patients’ immune system.

Patients experienced immune system–related adverse events, including mild flu-like symptoms, injection site reactions, rash, and fatigue.

At a median follow-up of 25 months (range, 20-32) following vaccination, 4 patients who had enrolled at stage IIIB/C did not have recurrence. However, 2 patients, who had a more advanced, lung metastatic disease, had disease recurrence. However, when these patients were subsequently treated with pembrolizumab, a programmed death ligand-1 inhibitor, they had a complete radiographic response after 4 doses that was ongoing at the time the paper was submitted.

Hailing the successful implementation of their strategy, the authors explain that a personal neoantigen vaccine can address 2 major challenges with cancer immunotherapy: targeting highly heterogenous tumors and selective targeting of the tumor over healthy tissue.

“Our vaccine is likely to target a diversity of malignant clones per patient, thus addressing tumor heterogeneity as well as minimizing the chance of tumor escape by loss of antigen,” they wrote.

Future trials will evaluate such personalized vaccines in combination with other immunotherapy agents, the authors conclude.

 
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