Abstract 3257: Unleashing immune power: How mRNA-encoded modulators suppress tumor growth

Abstract Subsequent to the emergence of the COVID-19 pandemic, an increased number of nucleic acid-based therapeutics have secured clinical endorsement. Unlike conventional protein-targeted therapies, nucleic acid therapeutics provide the potential for long-lasting effects and can be further categorized into oligonucleotides, single-guide RNA (sgRNA), and messenger RNA (mRNA). In this study, we aim to explore the anti-tumor properties of mRNA-encoded CD3-EpCAM Bispecific Antibody (BsAb) and mRNA-encoded IL-12 protein. We conducted qPCR, flow cytometry, and ELISA analysis to assess the dynamic concentration of mRNA-encoded CD3-EpCAM BsAb and mRNA-encoded IL-12 protein within tumor cells post-transfection. We then accessed their effects on anti-tumor and immune activation in vitro via flow cytometry and ELISA. Furthermore, using in vivo imaging system (IVIS), we were able to determine the biodistribution of mRNA-encoded BsAb in vivo. Efficacy was evaluated in subcutaneous tumor xenograft models with mRNA content in tumors examined via qPCR. Moreover, we analyzed the activation of tumor-infiltrating immune cells post mRNA-encoded IL-12 treatment. Finally, to ascertain the preliminary safety of mRNA-encoded BsAb and mRNA-encoded IL-12 protein, we conducted serum biochemistry analysis and histopathological examination of various organs. In this comprehensive preclinical evaluation, we found that both mRNA-encoded BsAb and mRNA-encoded IL-12 promoted the activation and cytotoxicity of human T cells, exhibiting significant inhibitory effects on tumor growth in vivo while maintaining a favorable safety profile. Our findings provide compelling evidence that mRNA therapeutics hold significant research value and exhibit promising potential for clinical applications. Citation Format: Dong Wang, zhixiang zhang, peili wang, binbin duan, xiangnan qiang, qingyang gu. Unleashing immune power: How mRNA-encoded modulators suppress tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3257.