Abstract 846: Circular RNA based cancer vaccine encoding NY-ESO-1 is effective for the treatment of lung cancer

Abstract Nucleic acid vaccines have undergone rapid development in recent years and are playing an increasingly prominent role in cancer therapy. Circular RNA (circRNA), with its unique closed-loop structure, extended protein expression half-life, enhanced stability, and simplified production process, represents a next-generation RNA carrier that offers significant advantages over traditional mRNA. In this study, we utilized our proprietary circRNA platform (NeoAna) to synthesize circRNA encoding NY-ESO-1, a highly immunogenic cancer-testis antigen expressed in various types of cancer, including lung cancer. This circRNA was delivered via lipid nanoparticles to develop a cancer vaccine. Our in vitro experiments demonstrated that circRNA encoding EGFP which was synthesized by NeoAna platform, achieved higher protein expression levels and prolonged expression duration in various cell lines compared to its mRNA counterpart. Moreover, NY-ESO-1 circRNA was found to effectively promote dendritic cell maturation, as well as T cell proliferation and activation in vitro. To assess the vaccine-induced anti-tumor immune responses, we collected spleens and lymph nodes from C57BL/6 mice following intramuscular vaccination. ELISpot assays and flow cytometry assays revealed that circRNA vaccine significantly increased the CD8/CD4 T cell ratio in these tissues, along with enhanced IFN-γ and TNF-α secretion by CD8+ and CD4+ T cells. Elevated NY-ESO-1-specific IgG antibody and IL-12 were confirmed by ELISA. In a murine lung cancer model established by subcutaneous injection of Lewis lung carcinoma cells overexpressing NY-ESO-1 into C57BL/6 mice, the circRNA vaccine demonstrated superior tumor suppression compared to an mRNA vaccine, with a higher proportion of antigen-specific T cells detected in peripheral blood. Additionally, histological examination of (H&E staining) and blood tests confirmed the safety of the circRNA vaccine for biological applications. In conclusion, our novel circRNA vaccine effectively activates anti-tumor immune responses and inhibits lung cancer progression, thereby providing a promising strategy for the clinical treatment of lung cancer. Citation Format: Shaoyi Chen, Mantang Qiu. Circular RNA based cancer vaccine encoding NY-ESO-1 is effective for the treatment of lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 846.