Ting Fan; Congcong Xu; Jichuan Wu; Yihua Cai; WuQiang Cao; Haifa Shen; Mingna Zhang; Hanfei Zhu; Jingxian Yang; Zhounan Zhu; Xiaopin Ma; Jiale Ren; Lei Huang; Qianyun Li; Yuying Tang; Bo Yu; Chunxiu Chen; Mingcheng Xu; Qiuhe Wang; Zhuya Xu; Fengjia Chen; Shujing Liang; Zhixian Zhong; Anmbreen Jamroze; Dean G. Tang; Hangwen Li; Chunyan Dong · 2024 · Science Advances
Paper
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.
Analysis
This study presents a lipopolyplex (LPP)-formulated mRNA cancer vaccine encoding tandem neoantigens that demonstrates robust neoantigen-specific T cell responses and significant antitumor activity in preclinical models and early clinical trials.
Discovery
Vladimir Zyrin; Evgeniy Mozheiko; Ivan Valiev; Alexey Lazarev; Tigran Gevorkyan; Matvey Murashko; Konstantin Okonechnikov
Ashling Cannon
Dinghai Zheng; Justin Hong; Jun Wang; Adrien Villain; Mickaël Costallat; Fernando Ulloa Montoya; Vikram Agarwal
Petar Brlek; Jan Kolić; Luka Bulić; Vedrana Škaro; Dragan Primorac
Almohanad A. Alkayyal
Crodel CC; Gork L; Göpel W; Linke P; Sinn K; Miethke J; Hochhaus A; Hilgendorf I
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