Abstract 3128: Nonclinical efficacy and safety evaluation of IL-12 mRNA delivered by a novel lipid nanoparticle

Abstract Interleukin-12 (IL-12) is considered to be a promising cytokine for enhancing anti-tumor immune response. However, systemic recombinant IL-12 had significant toxicity and limited efficacy in early clinical trials. Recently, many strategies to express IL-12 in the tumor tissue are being pursued preclinically and in clinical trials. Here, we report on ABO2011 (LNP-IL12 mRNA), developed by Abogen Bioscience, an innovative mRNA therapeutic cancer vaccine with novel lipid nanoparticles encoding IL-12.The LNP-IL12 mRNA significantly activates a robust T-cell-mediated adaptive immune response and exhibits strong anti-tumor potential. In the anti-tumor efficacy evaluation of B16F10, MC38 and EMT6 tumor-bearing mice, LNP-IL12 mRNA successfully eradicated tumors with a single administration. In the preliminary evaluation of safety, LNP-IL12 mRNA treatment did not significantly change body weight, HE staining of major organs did not significantly change, and serum cytokine levels were extremely low, indicating a good safety. Flow cytometry detected that LNP-IL12 mRNA induced large infiltration of total lymphocytes in B16F10, MC38 and EMT6 tumor-bearing mice, especially the proportion of cytotoxic CD8+ T cells and NK cells increased significantly, while the proportion of immunosuppressive Treg cells decreased. In addition, the levels of pro-inflammatory factors such as IL-1β, IL-6, IFN-γ and TNF-α in tumors induced by LNP-IL12 mRNA were significantly increased by CBA method, but IL-10 was not detected. It was shown that LNP-IL12 mRNA mediated immunotherapy can safely and effectively induce a strong immune response. In conclusion, we conducted relevant evaluation studies with LNP-mIL12 mRNA as an example, trying to establish non-clinical efficacy evaluation criteria for mRNA therapeutics. Citation Format: Qing He, Chunyan Dong, Dejiang Tan, Huimin Sun, Yiyang Zheng, Zhuang Li, Linyu Zhang, Sihan Liu, Yu Zhang, Jijun Yuan, Peng Gao, Liang Du, Huayuan Yan, Bo Ying. Nonclinical efficacy and safety evaluation of IL-12 mRNA delivered by a novel lipid nanoparticle. [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 3128.