mRNA vaccines in cancer immunotherapy: current progress and perspectives in solid tumors and hematologic malignancies

Abstract The unprecedented success of mRNA vaccines during the COVID-19 pandemic has accelerated the development of nucleic acid–based therapeutics, particularly in oncology. Decades of foundational research on mRNA design, delivery, and immunogenicity have laid the groundwork for the application of mRNA vaccines in cancer treatment. Herein, we summarize the key principles of synthetic mRNA engineering, including the optimization of structural elements, nucleoside modification, and codon usage to improve stability, enhance translation efficiency, and modulate immune responses. We highlight diverse antigen strategies, including tumor-associated antigens; neoantigens; and novel sources, such as cryptic antigens, aberrant splicing variants, and transposable element-derived antigens. We discuss delivery platforms, particularly lipid nanoparticles (LNPs) and dendritic cell-based systems, in the context of improving mRNA biodistribution and immune activation. We further examine how mRNA vaccines stimulate antitumor responses by encoding antigens, modulating the tumor microenvironment, and supporting adoptive T cell therapies. We review preclinical and clinical advances in combining mRNA vaccine with immune checkpoint inhibitors for the treatment of solid tumors (e.g., melanoma, pancreatic cancer, and glioblastoma) and hematologic malignancies (e.g., acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma). Finally, we explore emerging innovations, such as targeted LNP platforms for in vivo chimeric antigen receptor T/T cell receptor T engineering and artificial intelligence–assisted vaccine design, underscoring the transformative potential of mRNA technology in cancer immunotherapy.