TY - JOUR
T1 - From structural design to delivery
T2 - mRNA therapeutics for cancer immunotherapy
AU - Zhou, Feng
AU - Huang, Lujia
AU - Li, Shiqin
AU - Yang, Wenfang
AU - Chen, Fangmin
AU - Cai, Zhixiong
AU - Liu, Xiaolong
AU - Xu, Wujun
AU - Lehto, Vesa Pekka
AU - Lächelt, Ulrich
AU - Huang, Rongqin
AU - Shi, Yang
AU - Lammers, Twan
AU - Tao, Wei
AU - Xu, Zhi Ping
AU - Wagner, Ernst
AU - Xu, Zhiai
AU - Yu, Haijun
N1 - Publisher Copyright:
© 2023 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.
PY - 2024/4
Y1 - 2024/4
N2 - 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.
AB - 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.
KW - cancer immunotherapy
KW - cell-targeted delivery
KW - mRNA design
KW - mRNA therapeutics
KW - organ-specific delivery
UR - https://www.scopus.com/pages/publications/85184567720
U2 - 10.1002/EXP.20210146
DO - 10.1002/EXP.20210146
M3 - 文献综述
AN - SCOPUS:85184567720
SN - 2766-8509
VL - 4
JO - Exploration
JF - Exploration
IS - 2
M1 - 20210146
ER -