Predicted neoantigens from the CT26, MC38, and B16F10 mouse tumor models were encapsulated as mRNA in lipopolyplexes (LPPs). Injected s.c., the vaccine activated DCs and T cells, elicited neoantigen-specific and memory T cells, slowed tumor growth (dependent on CD8+ T cells), protected against tumor rechallenge, and synergized with anti-PD-1. 26/60 predicted neoantigens were immunogenic. Two human patients with advanced solid tumors were treated with a personalized LPP-mRNA vaccine (in combination with other therapies); treatment was safe, neoantigen-specific T cells were detected, and tumor outcomes were favorable.
Contributed by Alex Najibi
ABSTRACT: mRNA neoantigen cancer vaccine inducing neoantigen-specific T cell responses holds great promise for cancer immunotherapy; however, its clinical translation remains challenging because of suboptimal neoantigen prediction accuracy and low delivery efficiency, which compromise the in vivo therapeutic efficacy. We present a lipopolyplex (LPP)-formulated mRNA cancer vaccine encoding tandem neoantigens as a cancer therapeutic regimen. The LPP-formulated mRNA vaccines elicited robust neoantigen-specific CD8(+) T cell responses in three syngeneic murine tumor models (CT26, MC38, and B16F10) to suppress tumor growth. Prophylactic cancer vaccine treatment completely prevented tumor development, and long-lasting memory T cells protected mice from tumor cell rechallenge. Combining the vaccine with immune checkpoint inhibitor further boosted the antitumor activity. Of note, LPP-based personalized cancer vaccine was administered in two cancer patients and induced meaningful neoantigen-specific T cell and clinical responses. In conclusion, we demonstrated that the LPP-based mRNA vaccine can elicit strong antitumor immune responses, and the results support further clinical evaluation of the therapeutic mRNA cancer vaccine.
Author Info: (1) Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China. (2) StemiRNA Therapeutics Inc., Shanghai, China. Biomedical Polym
Author Info: (1) Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China. (2) StemiRNA Therapeutics Inc., Shanghai, China. Biomedical Polymers Laboratory, College of Chemistry Chemical Engineering and Materials Science and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China. International College of Pharmaceutical Innovation, Soochow University, Suzhou 215123, China. (3) StemiRNA Therapeutics Inc., Shanghai, China. Biomedical Polymers Laboratory, College of Chemistry Chemical Engineering and Materials Science and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China. College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. (4) StemiRNA Therapeutics Inc., Shanghai, China. (5) Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China. (6) StemiRNA Therapeutics Inc., Shanghai, China. (7) Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China. (8) StemiRNA Therapeutics Inc., Shanghai, China. (9) Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China. (10) Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China. (11) StemiRNA Therapeutics Inc., Shanghai, China. (12) StemiRNA Therapeutics Inc., Shanghai, China. (13) StemiRNA Therapeutics Inc., Shanghai, China. (14) StemiRNA Therapeutics Inc., Shanghai, China. (15) StemiRNA Therapeutics Inc., Shanghai, China. (16) StemiRNA Therapeutics Inc., Shanghai, China. (17) StemiRNA Therapeutics Inc., Shanghai, China. (18) StemiRNA Therapeutics Inc., Shanghai, China. (19) StemiRNA Therapeutics Inc., Shanghai, China. (20) StemiRNA Therapeutics Inc., Shanghai, China. (21) StemiRNA Therapeutics Inc., Shanghai, China. (22) Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China. (23) Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China. (24) Department of Pharmacology & Therapeutics and Experimental Therapeutics (ET) Graduate Program, University at Buffalo and Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. (25) Department of Pharmacology & Therapeutics and Experimental Therapeutics (ET) Graduate Program, University at Buffalo and Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. (26) StemiRNA Therapeutics Inc., Shanghai, China. (27) Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
