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ORIGINAL RESEARCH article

Front. Immunol.
Sec. T Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1531294
This article is part of the Research Topic Enhancing T Cell Function: Innovations in Cancer Immunotherapy View all 9 articles

A self-activated and protective (SAP) module enhances the preclinical performance of allogeneic anti-CD70 CAR-T cells

Provisionally accepted
Zhao Zhang Zhao Zhang 1Lianfeng Zhao Lianfeng Zhao 1*Tinghui Huang Tinghui Huang 1*Zhengliang Chen Zhengliang Chen 1*Yaoyao Zhao Yaoyao Zhao 1*Junqing Liang Junqing Liang 2*Xudong Ao Xudong Ao 2*Xiaoqiong Jia Xiaoqiong Jia 2*Lei Kang Lei Kang 2*Linghui Kong Linghui Kong 2Qi Jing Qi Jing 2*Jianhua Hu Jianhua Hu 3*Lili Gu Lili Gu 4*Feiyan Pan Feiyan Pan 1Zhigang Hu Zhigang Hu 1Lingfeng He Lingfeng He 1Muya Zhou Muya Zhou 1*Jiannan Chen Jiannan Chen 1*Zhigang Guo Zhigang Guo 1*
  • 1 Nanjing Normal University, Nanjing, China
  • 2 Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
  • 3 Jiangsu Province Geriatric Hospital, Nanjing, Jiangsu Province, China
  • 4 Nanjing CalmHome Institute of Cell and Gene Engineering, Nanjing, China

The final, formatted version of the article will be published soon.

    Allogeneic chimeric antigen receptor T (CAR-T) therapy, also known as universal CAR-T (UCAR-T) therapy, offers broad applicability, high production efficiency, and reduced costs, enabling quicker access for patients. However, clinical application remains limited by challenges such as immune rejection, and issues with potency and durability. To address these limitations, we developed an 'all-in-one' self-activated and protective (SAP) module, integrated into the CAR scaffold. The SAP module consists of the CD47 extracellular domain, a mutant interleukin 7 receptor alpha (IL7Rα) transmembrane domain, and the IL7Rα intracellular domain, designed to protect UCAR-T cells from host immune attacks and enhance their survival. As anticipated, SAP UCAR-T cells experienced reduced immune rejection from the innate immune system, showed improved persistence and functionality both in vitro and in vivo, and raised no safety concerns. Moreover, the process stability of SAP UCAR-T cells was demonstrated in scale-up production. Overall, our findings highlight the SAP module as a promising strategy for the preclinical development of anti-CD70 UCAR-T, paving the way for an 'off-the-shelf' cell therapy product.

    Keywords: chimeric antigen receptor T (CAR-T), allogeneic CAR-T, cancer immunotherapy, Solid tumor, CD70-positive cancer

    Received: 20 Nov 2024; Accepted: 30 Dec 2024.

    Copyright: © 2024 Zhang, Zhao, Huang, Chen, Zhao, Liang, Ao, Jia, Kang, Kong, Jing, Hu, Gu, Pan, Hu, He, Zhou, Chen and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Lianfeng Zhao, Nanjing Normal University, Nanjing, China
    Tinghui Huang, Nanjing Normal University, Nanjing, China
    Zhengliang Chen, Nanjing Normal University, Nanjing, China
    Yaoyao Zhao, Nanjing Normal University, Nanjing, China
    Junqing Liang, Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
    Xudong Ao, Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
    Xiaoqiong Jia, Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
    Lei Kang, Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
    Qi Jing, Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China
    Jianhua Hu, Jiangsu Province Geriatric Hospital, Nanjing, 210024, Jiangsu Province, China
    Lili Gu, Nanjing CalmHome Institute of Cell and Gene Engineering, Nanjing, China
    Muya Zhou, Nanjing Normal University, Nanjing, China
    Jiannan Chen, Nanjing Normal University, Nanjing, China
    Zhigang Guo, Nanjing Normal University, Nanjing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.