TY - JOUR
T1 - HER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer
AU - Xu, Jie
AU - Meng, Qingtao
AU - Sun, Hao
AU - Zhang, Xinwei
AU - Yun, Jun
AU - Li, Bin
AU - Wu, Shenshen
AU - Li, Xiaobo
AU - Yang, Hongbao
AU - Zhu, Haitao
AU - Aschner, Michael
AU - Relucenti, Michela
AU - Familiari, Giuseppe
AU - Chen, Rui
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41419-021-04100-0
DO - 10.1038/s41419-021-04100-0
M3 - Article
C2 - 34839348
AN - SCOPUS:85120089484
SN - 2041-4889
VL - 12
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 12
M1 - 1109
ER -
