NEOANTIGEN DNA vaccines show promise in treating triple-negative breast cancer, with high safety, robust immune responses, and encouraging recurrence-free survival rates at 36 months.
Triple-negative breast cancer is a challenging subtype of breast cancer, often associated with poor outcomes, particularly in patients with residual disease following neoadjuvant chemotherapy. Neoantigen vaccines offer a personalised immunotherapy approach, leveraging tumour-specific mutations to elicit targeted immune responses. This study aimed to assess the safety, feasibility, and efficacy of a novel neoantigen DNA vaccine in a phase 1 trial involving patients at high risk of recurrence.
In this trial, tumour and normal tissues underwent exome and RNA sequencing to identify somatic mutations and prioritise neoantigens using the pVACtools suite. Vaccines were customised for each patient, encoding an average of 11 neoantigens, and administered via electroporation in the adjuvant setting after surgical tumour removal and standard therapy. Eighteen patients received three doses, and immune responses were assessed using ELISpot, flow cytometry, and TCR sequencing. Results demonstrated vaccine safety, with minimal adverse events and robust immune activation in 14 of 18 patients. Median follow-up at 36 months revealed an 87.5% recurrence-free survival rate (95% CI: 72.7–100%), highlighting the vaccine’s potential efficacy.
These findings highlight the potential of neoantigen DNA vaccines as a safe and effective strategy for enhancing antitumour immunity in triple-negative breast cancer. The high recurrence-free survival rate observed warrants further investigation in larger, randomised studies. Clinically, this vaccine platform could serve as a transformative adjuvant therapy, offering a personalised and targeted approach for high-risk patients. Future efforts should focus on optimising vaccine design, delivery mechanisms, and combining this therapy with immune checkpoint inhibitors to further improve outcomes.
Reference
Zhang X et al. Neoantigen DNA vaccines are safe, feasible, and induce neoantigen-specific immune responses in triple-negative breast cancer patients. Genome Med. 2024;16:131.
