Neoadjuvant personalized viral vaccine prevents tumor relapse in checkpoint-resistant murine melanoma model.

backgroundPersonalized cancer vaccines targeting tumor-specific neoantigens (nAgs) are an emerging therapeutic strategy, particularly effective in early-stage disease before immune suppression is established. Immune checkpoint inhibitors have demonstrated benefit in the adjuvant setting (postsurgery), and recent evidence suggests neoadjuvant administration (before surgery) may further enhance antitumor immunity. This study evaluated the efficacy of a multiepitope nAg vaccine in a preclinical melanoma model resistant to checkpoint inhibition, comparing neoadjuvant and adjuvant treatment, alone or in combination with anti-programmed cell death protein 1 (PD1) therapy.

methodsA viral vector nAg vaccine was developed and administered in the B16F10 murine melanoma model. Mice received the vaccine either before (neoadjuvant) or after (adjuvant) tumor resection alone or in combination with anti-PD1. Tumor recurrence and survival were assessed. Immune profiling was performed to evaluate T cell phenotypes, and CD8

resultsNeoadjuvant vaccination alone provided approximately 70% protection against tumor recurrence. When combined with anti-PD1, protection increased to 90%. Notably, anti-PD1 alone conferred 60% protection when used in a neoadjuvant setting. In contrast, adjuvant vaccination was ineffective as monotherapy and required combination with anti-PD1 to prevent relapse. The efficacy of neoadjuvant vaccination was dependent on CD8

conclusionsNeoadjuvant nAg vaccination elicits potent CD8