Therapeutic vaccines targeting solid tumors: A series of clinical trial analysis over the past decade.

Therapeutic cancer vaccines hold great promise, yet their clinical efficacy in solid tumors remains modest. We systematically analyzed 86 clinical trials published between 2015 and 2025 evaluating therapeutic vaccines across mRNA, DNA, peptide, dendritic cell, virus vector, and whole tumor cell platforms to understand their clinical utility and key challenges in development. Peptide-based vaccines dominated, while mRNA vaccines showed the fastest growth, often combined with immune checkpoint inhibitors. Among 1588 patients with advanced disease, the disease control rate was 53 % and the objective response rate 18 %. In adjuvant settings, 52 % of 461 patients experienced recurrence. Although 67 % exhibited ELISPOT-positive T-cell responses, no correlation with clinical efficacy was observed. Most adverse events were mild to moderate, with pyrexia, fatigue, and injection-site reactions predominating. Therapeutic vaccines thus demonstrate favorable safety and immunogenicity, but limited monotherapy efficacy, underscoring the need for combinatorial approaches and identifying personalized immunogenic neoantigens to enhance clinical benefit.