From structural design to delivery: mRNA therapeutics for cancer immunotherapy
Feng Zhou,
Lujia Huang,
Shiqin Li,
Wenfang Yang,
Fangmin Chen,
Zhixiong Cai,
Xiaolong Liu,
Wujun Xu,
Vesa‐Pekka Lehto,
Ulrich Lächelt,
Rongqin Huang,
Yang Shi,
Twan Lammers,
Wei Tao,
Zhi Ping Xu,
Ernst Wagner,
Zhiai Xu,
Haijun Yu
Affiliations
Feng Zhou
State Key Laboratory of Chemical Biology and Center of Pharmaceutics, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China
Lujia Huang
State Key Laboratory of Chemical Biology and Center of Pharmaceutics, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China
Shiqin Li
State Key Laboratory of Chemical Biology and Center of Pharmaceutics, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China
Wenfang Yang
State Key Laboratory of Chemical Biology and Center of Pharmaceutics, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China
Fangmin Chen
State Key Laboratory of Chemical Biology and Center of Pharmaceutics, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China
Zhixiong Cai
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou China
Xiaolong Liu
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou China
Wujun Xu
Department of Applied Physics University of Eastern Finland Kuopio Finland
Vesa‐Pekka Lehto
Department of Applied Physics University of Eastern Finland Kuopio Finland
Ulrich Lächelt
Department of Pharmaceutical Sciences University of Vienna Vienna Austria
Rongqin Huang
Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery Ministry of Education, Fudan University Shanghai China
Yang Shi
Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging RWTH Aachen University Clinic Aachen Germany
Twan Lammers
Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging RWTH Aachen University Clinic Aachen Germany
Wei Tao
Center for Nanomedicine and Department of Anaesthesiology, Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA
Zhi Ping Xu
Institute of Biomedical Health Technology and Engineering and Institute of Systems and Physical Biology Shenzhen Bay Laboratory Shenzhen China
Ernst Wagner
Pharmaceutical Biotechnology, Center for Nanoscience Ludwig‐Maximilians‐Universität Munich Germany
Zhiai Xu
School of Chemistry and Molecular Engineering East China Normal University Shanghai China
Haijun Yu
State Key Laboratory of Chemical Biology and Center of Pharmaceutics, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China
Abstract mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority in expressing all sequence‐known proteins in vivo. In particular, with a small dosage of delivered mRNA, antigen‐presenting cells (APCs) can synthesize mutant neo‐antigens and multi‐antigens and present epitopes to T lymphocytes to elicit antitumor effects. In addition, expressing receptors like chimeric antigen receptor (CAR), T‐cell receptor (TCR), CD134, and immune‐modulating factors including cytokines, interferons, and antibodies in specific cells can enhance immunological response against tumors. With the maturation of in vitro transcription (IVT) technology, large‐scale and pure mRNA encoding specific proteins can be synthesized quickly. However, the clinical translation of mRNA‐based anticancer strategies is restricted by delivering mRNA into target organs or cells and the inadequate endosomal escape efficiency of mRNA. Recently, there have been some advances in mRNA‐based cancer immunotherapy, which can be roughly classified as modifications of the mRNA structure and the development of delivery systems, especially the lipid nanoparticle platforms. In this review, the latest strategies for overcoming the limitations of mRNA‐based cancer immunotherapies and the recent advances in delivering mRNA into specific organs and cells are summarized. Challenges and opportunities for clinical applications of mRNA‐based cancer immunotherapy are also discussed.
