Potential of Circular RNAs (circRNAs) Neoantigen Vaccines in Tumor Immunotherapy.

Abstract

Circular RNAs (circRNAs) have emerged as promising candidates for neoantigen vaccine development due to their unique structural stability, enhanced translational efficiency, and immunostimulatory properties. Unlike linear RNAs, circRNAs exhibit exonuclease resistance, prolonged antigen expression, and increased activation of innate immune receptors such as RIG-I and MDA5, thereby enhancing anti-tumor immune responses. Preclinical studies have demonstrated that circRNA-based vaccines encoding tumor-specific neoantigens effectively stimulate Antigen- Presenting Cells (APCs), particularly Dendritic Cells (DCs), leading to robust CD8+ Cytotoxic T Lymphocyte (CTL) activation. This results in increased cytokine production, T-cell proliferation, and durable anti-tumor immunity. Compared to conventional neoantigen vaccine platforms, circRNA vaccines offer distinct advantages, including higher immunogenicity, improved cytosolic delivery, and minimal risk of genomic integration. CircRNA vaccines have demonstrated efficacy in preclinical tumor models, with studies highlighting their ability to induce long-term memory T-- cell responses and enhance the efficacy of immune checkpoint blockade therapies. However, challenges remain in optimizing circRNA delivery, mitigating unintended immune activation, and scaling up manufacturing processes. The translational potential of circRNA vaccines in tumor immunotherapy is significant, offering a novel and scalable approach to personalized cancer treatment. Further research and clinical validation are needed to optimize their design, improve manufacturing efficiency, and assess their efficacy in human trials. CircRNA vaccines represent a next-- generation platform with the potential to revolutionize cancer immunotherapy by harnessing durable and targeted anti-tumor immune responses.