1172 Human TROP2 protein and circRNA vaccines inhibit tumor growth in TROP2-humanized mouse models

作者：Zirong He, Fanyan Meng, Chi Han Samson Li, Ning Lin, Melvin Toh, Hong Wang · 发表于：Regular and Young Investigator Award Abstracts · 年份：2025 · DOI：10.1136/jitc-2025-sitc2025.1172 · 被引用次数：1 · 研究领域：Circular RNAs in diseases、Cancer Mechanisms and Therapy、interferon and immune responses

Background Human trophoblast cell surface antigen 2 (hTROP2), a transmembrane glycoprotein encoded by the Tumor Associated Calcium Signal Transducer 2 (TACSTD2) gene, is primarily expressed in trophoblasts and minimally in a few adult tissues. In various cancers, hTROP2 is overexpressed, making it a promising target for cancer immunotherapy. Here, we developed hTROP2 protein and circular mRNA-lipid nanoparticle (circRNA-LNP) vaccines and evaluated their efficacy in activating cellular immunity and suppressing hTROP2+ tumors in mice.Methods Recombinant protein antigens, consisting of hTROP2 fragments with or without immune enhancers, were produced in E. coli and 293T cells. The circRNA-LNP vaccine was prepared using standard in vitro transcription, circularization, and LNP-packaging methods. Mice were vaccinated with either protein antigen adjuvanted with a mixture of Poly(I:C) and Complete/Incomplete Freund’s Adjuvant by subcutaneous injection once a week for seven weeks or circRNA-LNP by one or two intramuscular injections. Cellular immunity was assessed by the INFγ ELISpot assay using splenocytes. Anti-cancer efficacy was evaluated by monitoring tumor growth of TROP2-humanized mouse cancer cells, MC38-hTROP2 or 4T1-hTROP2, inoculated subcutaneously in mice that received vaccine or control.Results hTROP2 vaccines demonstrated robust activity in activating cellular immunity in both wildtype and several HLA-I allele-humanized transgenic mice. Two highly immunogenic fragments, ...