Advances in mRNA therapeutics for cancer immunotherapy: From modification to delivery

Geonhee Han; Dahye Noh; Hokyung Lee; Sangmin Lee; Sehoon Kim; Hong Yeol Yoon; Soo Hyeon Lee

doi:10.1016/j.addr.2023.114973

Advances in mRNA therapeutics for cancer immunotherapy: From modification to delivery

Adv Drug Deliv Rev. 2023 Aug:199:114973. doi: 10.1016/j.addr.2023.114973. Epub 2023 Jun 25.

Authors

Geonhee Han¹, Dahye Noh², Hokyung Lee³, Sangmin Lee⁴, Sehoon Kim⁵, Hong Yeol Yoon⁶, Soo Hyeon Lee⁷

Affiliations

¹ KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea; Medicinal Materials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea.
² Medicinal Materials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea; Division of Bio-Medical Science &Technology, KIST School, University of Science and Technology, Hwarang-ro14-gil 5, Seongbuk-gu, Seoul, Republic of Korea 02792; Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
³ Medicinal Materials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Fundamental Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 02447, Republic of Korea.
⁴ Department of Fundamental Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 02447, Republic of Korea.
⁵ KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea; Department of Fundamental Pharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 02447, Republic of Korea.
⁶ Medicinal Materials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Republic of Korea; Division of Bio-Medical Science &Technology, KIST School, University of Science and Technology, Hwarang-ro14-gil 5, Seongbuk-gu, Seoul, Republic of Korea 02792. Electronic address: seerou@kist.re.kr.
⁷ Molecular Surgery Laboratory, Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, CA 94304, USA. Electronic address: soohyeon@stanford.edu.

Abstract

RNA vaccines have demonstrated their ability to solve the issues posed by the COVID-19 pandemic. This success has led to the renaissance of research into mRNA and their nanoformulations as potential therapeutic modalities for various diseases. The potential of mRNA as a template for synthesizing proteins and protein fragments for cancer immunotherapy is now being explored. Despite the promise, the use of mRNA in cancer immunotherapy is limited by challenges, such as low stability against extracellular RNases, poor delivery efficiency to the target organs and cells, short circulatory half-life, variable expression levels and duration. This review highlights recent advances in chemical modification and advanced delivery systems that are helping to address these challenges and unlock the biological and pharmacological potential of mRNA therapeutics in cancer immunotherapy. The review concludes by discussing future perspectives for mRNA-based cancer immunotherapy, which holds great promise as a next-generation therapeutic modality.

Keywords: Cancer immunotherapy; Chemical modification; RNA drug; mRNA; mRNA delivery.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19* / therapy
Humans
Immunotherapy
Neoplasms*
Pandemics
Proteins
RNA, Messenger

Substances

RNA, Messenger
Proteins