HER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer

Jie Xu, Qingtao Meng, Hao Sun, Xinwei Zhang, Jun Yun, Bin Li, Shenshen Wu, Xiaobo Li, Hongbao Yang, Haitao Zhu, Michael Aschner, Michela Relucenti, Giuseppe Familiari, Rui Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Chimeric antigen receptor (CAR) - T cell therapy is a new class of cellular immunotherapies, which has made great achievements in the treatment of malignant tumors. Despite improvements in colorectal cancer (CRC) therapy, treatment of many patients fails because of metastasis and recurrence. The human epidermal growth factor receptor 2 (HER2) is a substantiated target for CAR-T therapy, and has been reported recently to be over-expressed in CRC, which may provide a potential therapeutic target for CRC treatment. Herein, HER2 was a promising target of metastatic colorectal cancer (mCRC) in CAR-T therapy as assessed by flow cytometry and tissue microarray (TMA) with 9-year survival follow-up data. Furthermore, HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting ability against CRC cells in vitro. Moreover, through the tumor-bearing model of the NOD-Prkdcem26cd52Il2rgem26Cd22/Nju (NCG) mice, HER2 CAR-T cells showed signs of effectively preventing CRC progression in three different xenograft models. Notably, HER2 CAR-T cells displayed greater aggressiveness in HER2+ CRC in the patient-derived tumor xenograft (PDX) models and had potent immunotherapeutic capacity for mCRC in the metastatic xenograft mouse models. In conclusion, our studies provide scientific evidence that HER2 CAR-T cells represent an emerging immunotherapy for the treatment of mCRC.

Original languageEnglish (US)
Article number1109
JournalCell Death and Disease
Volume12
Issue number12
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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