A multi-adjuvant personal neoantigen vaccine generates potent immunity in melanoma.
Level 4 - case-series / case-control
Uncontrolled single-arm phase I clinical trial
PubMed 40645179 · doi:10.1016/j.cell.2025.06.019
What was done
Ten patients with melanoma were evaluated in a phase I trial testing a personalized synthetic long peptide vaccine formulated with Montanide, poly-ICLC, and locally administered ipilimumab alongside systemic nivolumab. The study evaluated de novo ex vivo T cell responses against immunizing neoepitopes and tracked circulating and intratumoral T cell receptor (TCR) clonotypes using single-cell phenotypic analysis.
What was found
De novo ex vivo T cell responses against the majority of immunizing neoepitopes were induced in all 9 fully vaccinated patients, with ex vivo CD8+ T cell responses observed in 6 of 9 patients. Vaccination induced hundreds of circulating and intratumoral TCR clonotypes distinct from those arising after PD-1 inhibition, remodeling the intratumoral T cell repertoire. Clinical efficacy and survival metrics were not reported in the abstract.
Why it matters
This study demonstrates that multi-pronged immune adjuvant strategies combined with local and systemic checkpoint blockade can elicit broad, tumor-infiltrating neoepitope-specific T cell responses in melanoma.
Limits
The study is small (n = 10 enrolled, 9 fully vaccinated) and non-randomized with no comparator group. Clinical endpoints such as progression-free or overall survival and safety outcomes are not reported in the abstract.
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