Synergistic Antitumor Activity of Personalized mRNA Neoantigen Vaccines and PD-1/PD-L1 Inhibitor in Solid Tumors

Abstract

Immunotherapy for cancer now represents a breakthrough in treatment of solid tumors. However, the clinical efficacy of immune checkpoint inhibitors is still limited by insufficient tumor-specific immune activation and multiple immune escape mechanisms. Personalized mRNA vaccines based on neoantigens offer an encouraging way to deal with such limitations, since they may elicit individualized T-cell activity against each person's specific tumor antigens. This paper reviews the synergistic anti-tumor potential of combining personalized mRNA neoantigen vaccines with Programmed Cell Death Protein-1/ Programmed Cell Death Ligand Protein-1(PD-1/PD-L1) inhibitors in solid tumors. Firstly, the complementary mechanisms underlying this combination are discussed. Current clinical evidence from melanoma, pancreatic ductal adenocarcinoma, renal cell carcinoma, and other solid tumor types shows that this strategy may elicit a durable tumor-specific immune response, which is particularly encouraging in the context of adjuvant therapy and minimal residual disease (MRD). However, due to differences in tumor mutation burden, antigen-presenting ability, immune cell infiltration, and the tumor microenvironment, treatment efficacy still varies among different tumor types. Moreover, clinical translation is also limited by the lack of large - scale clinical data, the scarcity of predictive biomarkers, the high complexity of personalized production, and challenges in cost and accessibility. Future advancements in neoantigen prediction, mRNA delivery technology, biomarker-based patient selection, and rational combination therapy will be essential for achieving more accurate treatment and for extending the use of personalized cancer immunotherapy in practice.