From structural design to delivery: mRNA therapeutics for cancer immunotherapy

Author:

Zhou Feng12,Huang Lujia12,Li Shiqin1,Yang Wenfang1,Chen Fangmin12,Cai Zhixiong3,Liu Xiaolong3ORCID,Xu Wujun4,Lehto Vesa‐Pekka4,Lächelt Ulrich5ORCID,Huang Rongqin6,Shi Yang7,Lammers Twan7,Tao Wei8ORCID,Xu Zhi Ping9,Wagner Ernst10,Xu Zhiai11,Yu Haijun12ORCID

Affiliation:

1. State Key Laboratory of Chemical Biology and Center of Pharmaceutics, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China

2. University of Chinese Academy of Sciences Beijing China

3. The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou China

4. Department of Applied Physics University of Eastern Finland Kuopio Finland

5. Department of Pharmaceutical Sciences University of Vienna Vienna Austria

6. Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery Ministry of Education, Fudan University Shanghai China

7. Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging RWTH Aachen University Clinic Aachen Germany

8. Center for Nanomedicine and Department of Anaesthesiology, Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA

9. Institute of Biomedical Health Technology and Engineering and Institute of Systems and Physical Biology Shenzhen Bay Laboratory Shenzhen China

10. Pharmaceutical Biotechnology, Center for Nanoscience Ludwig‐Maximilians‐Universität Munich Germany

11. School of Chemistry and Molecular Engineering East China Normal University Shanghai China

Abstract

AbstractmRNA 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.

Funder

Science and Technology Commission of Shanghai Municipality

National Natural Science Foundation of China

Publisher

Wiley

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