Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-targeting Intracellular Checkpoint CISH

Sunil Kumar
* ORCID logo ,
Parth Sarthi
,
Indra Mani
ORCID logo ,
Muhammad Umer Ashraf
,
Myeong-Ho Kang
,
Vishal Kumar
,
Yong-Soo Bae
* ORCID logo
Version 1 : Received: 3 August 2021 / Approved: 4 August 2021 / Online: 4 August 2021 (13:02:22 CEST)

A peer-reviewed article of this Preprint also exists.

Kumar, S.; Sarthi, P.; Mani, I.; Ashraf, M.U.; Kang, M.-H.; Kumar, V.; Bae, Y.-S. Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-targeting Intracellular Checkpoint CISH. Cells 2021, 10, 2250. Kumar, S.; Sarthi, P.; Mani, I.; Ashraf, M.U.; Kang, M.-H.; Kumar, V.; Bae, Y.-S. Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-targeting Intracellular Checkpoint CISH. Cells 2021, 10, 2250.

Abstract

Cellular immunotherapy has recently emerged as a fourth pillar in cancer treatment co-joining surgery, chemotherapy and radiotherapy. Where, the discovery of immune checkpoint blockage or inhibition (ICB/ICI), anti-PD-1/PD-L1 and anti-CTLA4-based, therapy has revolutionized the class of cancer treatment at a different level. However, still some cancer patient escape this immune surveillance mechanism and become resistant to ICB-therapy. Therefore, a more advanced or an alternative treatment is required instantly. Despite the functional importance of epitranscriptomics in diverse clinico-biological practices, its role in improving the efficacy of ICB therapeutics has been limited. Consequently, our study encapsulates the evidences, as a possible strategy, to improve the efficacy of ICB-therapy by co-targeting molecular checkpoints especially N6A-modification machineries which could be reformed into RNA modifying drugs (RMD). Here, we have explained the mechanism of individual RNA-modifiers (editor/writer, eraser/remover and effector/reader) in overcoming the issues associated with high-dose antibody toxicities and drug-resistance. Moreover, we have shed light on the importance of suppressor of cytokine signalling (SOCS/CISH) and microRNAs in improving the efficacy of ICB-therapy, with brief insight on the current monoclonal antibodies undergoing clinical trials or already approved against several solid tumor and metastatic cancers. We anticipate our investigation will encourage researchers and clinicians to further strengthen the efficacy of ICB-therapeutics by considering the importance of epitranscriptomics as a personalized medicine.

Keywords

Epitranscriptomics, Immune checkpoint blockage (ICB) therapy, anti-PD-1/PD-L1 drug resistance, Personalized medicine, CISH, microRNAs

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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