Researchers Evaluate Novel Circular RNA Vaccine for Lung Cancer

A novel circular RNA vaccine may be a “promising strategy for the clinical treatment of lung cancer,” according to research presented at the American Association for Cancer Research Annual Meeting 2025.

A team from Peking University People’s Hospital conducted the study and presented the findings, explaining that nucleic acid vaccines “have undergone rapid development in recent years and are playing an increasingly prominent role in cancer therapy.”

Circular RNA, which has a “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,” according to the study authors.

In the study presented, the research team used its proprietary circular RNA platform, NeoAna, to synthesize circular RNA encoding NY-ESO-1, which is a “highly immunogenic cancer-testis antigen expressed in various types of cancer, including lung cancer.” The circular RNA was delivered through lipid nanoparticles to develop a cancer vaccine.

The researchers in vitro experiments showed that circular RNA encoding EGFP synthesized by NeoAna platform “achieved higher protein expression levels and prolonged-expression duration in various cell lines compared to its mRNA counterpart,” they explained. In addition, the in vitro research showed that NY-ESO-1 circular RNA promoted dendritic cell maturation and T cell proliferation and activation.

The researchers also assessed vaccine-induced antitumor immune responses by collecting spleens and lymph nodes from C57BL/6 mice after the mice underwent intramuscular vaccination. The circular RNA vaccine “significantly increased” the CD8/CD4 T cell ratio in these tissues and showed “enhanced” IFN-γ and TNF-α secretion by CD8-positive and CD4-positive T cells, ELISpot and flow cytometry analyses showed. The researchers used ELISA to confirm the elevated NY-ESO-1-specific IgG antibody and IL-12.

In addition, the study investigators assessed the circular RNA vaccine in mice. The mouse model of lung cancer was established by subcutaneously injecting C57BL/6 mice with Lewis lung carcinoma cells overexpressing NY-ESO-1. In mice, the circular RNA vaccine “demonstrated superior tumor suppression compared to an mRNA vaccine, with a higher proportion of antigen-specific T cells detected in peripheral blood,” according to the researchers. They also conducted histological examinations and blood tests, which “confirmed the safety” of the circular RNA vaccine for biological applications.

“In conclusion, our novel [circular] RNA vaccine effectively activates anti-tumor immune responses and inhibits lung cancer progression, thereby providing a promising strategy for the clinical treatment of lung cancer,” the study authors explained.

Reference

American Association for Cancer Research Annual Meeting 2025. Abstract #846. https://aacrjournals.org/cancerres/article/85/8_Supplement_1/846/756030/Abstract-846-Circular-RNA-based-cancer-vaccine