The exosomes derived from CAR-T cell efficiently target mesothelin and reduce triple-negative breast cancer growth

Pengxiang Yang; Xingjian Cao; Huilong Cai; Panfeng Feng; Xiang Chen; Yihua Zhu; Yue Yang; Weiwei An; Yumin Yang; Jing Jie

doi:10.1016/j.cellimm.2020.104262

The exosomes derived from CAR-T cell efficiently target mesothelin and reduce triple-negative breast cancer growth

Pengxiang Yang
, Xingjian Cao
, Huilong Cai
, Panfeng Feng
, Xiang Chen
, Yihua Zhu
, Yue Yang
, Weiwei An
, Yumin Yang^*
, Jing Jie^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

167 Citations (Scopus)

Abstract

Genetically engineered T cells expressing a chimeric antigen receptor (CAR) have rapidly developed into a powerful and innovative therapeutic modality for cancer patients. However, the problem of dose-dependent systemic toxicity cannot be ignored. In this study, exosomes derived from mesothelin (MSLN)-targeted CAR-T cells were isolated, and we found that they maintain most characteristics of the parental T cells, including surface expression of the CARs and CD3. Furthermore, CAR-carrying exosomes significantly inhibited the growth of both endogenous and exogenous MSLN-positive triple-negative breast cancer (TNBC) cells. The expression of the effector molecules perforin and granzyme B may be a mechanism of tumor killing. More importantly, a highly effective tumor inhibition rate without obvious side effects was observed with the administration of CAR-T cell exosomes in vivo. Thus, the use of CAR-T cell exosomes has great therapeutic potential against MSLN-expressing TNBC. © 2020 Elsevier Inc.

Original language	English
Article number	104262
Journal	Cellular Immunology
Volume	360
Online published	18 Dec 2020
DOIs	https://doi.org/10.1016/j.cellimm.2020.104262
Publication status	Published - Feb 2021
Externally published	Yes

Funding

This work was supported by National Natural Science Foundation of China (No. 31900987 ), Heilongjiang Natural Science Foundation (No. YQ2019H022 ), Nantong Science and Technology Plan Project (No. JC2019146 ) and Nantong University Clinical Medicine Project (No. 2019JZ004 ).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

CAR-T
Exosomes
Mesothelin
Triple-negative breast cancer
Tumor immunotherapy

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10.1016/j.cellimm.2020.104262

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@article{ab4aa00f69a1457fad0f27b00fe5a54a,

title = "The exosomes derived from CAR-T cell efficiently target mesothelin and reduce triple-negative breast cancer growth",

abstract = "Genetically engineered T cells expressing a chimeric antigen receptor (CAR) have rapidly developed into a powerful and innovative therapeutic modality for cancer patients. However, the problem of dose-dependent systemic toxicity cannot be ignored. In this study, exosomes derived from mesothelin (MSLN)-targeted CAR-T cells were isolated, and we found that they maintain most characteristics of the parental T cells, including surface expression of the CARs and CD3. Furthermore, CAR-carrying exosomes significantly inhibited the growth of both endogenous and exogenous MSLN-positive triple-negative breast cancer (TNBC) cells. The expression of the effector molecules perforin and granzyme B may be a mechanism of tumor killing. More importantly, a highly effective tumor inhibition rate without obvious side effects was observed with the administration of CAR-T cell exosomes in vivo. Thus, the use of CAR-T cell exosomes has great therapeutic potential against MSLN-expressing TNBC. {\textcopyright} 2020 Elsevier Inc.",

keywords = "CAR-T, Exosomes, Mesothelin, Triple-negative breast cancer, Tumor immunotherapy",

author = "Pengxiang Yang and Xingjian Cao and Huilong Cai and Panfeng Feng and Xiang Chen and Yihua Zhu and Yue Yang and Weiwei An and Yumin Yang and Jing Jie",

year = "2021",

month = feb,

doi = "10.1016/j.cellimm.2020.104262",

language = "English",

volume = "360",

journal = "Cellular Immunology",

issn = "0008-8749",

publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - The exosomes derived from CAR-T cell efficiently target mesothelin and reduce triple-negative breast cancer growth

AU - Yang, Pengxiang

AU - Cao, Xingjian

AU - Cai, Huilong

AU - Feng, Panfeng

AU - Chen, Xiang

AU - Zhu, Yihua

AU - Yang, Yue

AU - An, Weiwei

AU - Yang, Yumin

AU - Jie, Jing

PY - 2021/2

Y1 - 2021/2

N2 - Genetically engineered T cells expressing a chimeric antigen receptor (CAR) have rapidly developed into a powerful and innovative therapeutic modality for cancer patients. However, the problem of dose-dependent systemic toxicity cannot be ignored. In this study, exosomes derived from mesothelin (MSLN)-targeted CAR-T cells were isolated, and we found that they maintain most characteristics of the parental T cells, including surface expression of the CARs and CD3. Furthermore, CAR-carrying exosomes significantly inhibited the growth of both endogenous and exogenous MSLN-positive triple-negative breast cancer (TNBC) cells. The expression of the effector molecules perforin and granzyme B may be a mechanism of tumor killing. More importantly, a highly effective tumor inhibition rate without obvious side effects was observed with the administration of CAR-T cell exosomes in vivo. Thus, the use of CAR-T cell exosomes has great therapeutic potential against MSLN-expressing TNBC. © 2020 Elsevier Inc.

AB - Genetically engineered T cells expressing a chimeric antigen receptor (CAR) have rapidly developed into a powerful and innovative therapeutic modality for cancer patients. However, the problem of dose-dependent systemic toxicity cannot be ignored. In this study, exosomes derived from mesothelin (MSLN)-targeted CAR-T cells were isolated, and we found that they maintain most characteristics of the parental T cells, including surface expression of the CARs and CD3. Furthermore, CAR-carrying exosomes significantly inhibited the growth of both endogenous and exogenous MSLN-positive triple-negative breast cancer (TNBC) cells. The expression of the effector molecules perforin and granzyme B may be a mechanism of tumor killing. More importantly, a highly effective tumor inhibition rate without obvious side effects was observed with the administration of CAR-T cell exosomes in vivo. Thus, the use of CAR-T cell exosomes has great therapeutic potential against MSLN-expressing TNBC. © 2020 Elsevier Inc.

KW - CAR-T

KW - Exosomes

KW - Mesothelin

KW - Triple-negative breast cancer

KW - Tumor immunotherapy

UR - https://www.scopus.com/pages/publications/85098153883

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85098153883&origin=recordpage

U2 - 10.1016/j.cellimm.2020.104262

DO - 10.1016/j.cellimm.2020.104262

M3 - RGC 21 - Publication in refereed journal

C2 - 33373818

SN - 0008-8749

VL - 360

JO - Cellular Immunology

JF - Cellular Immunology

M1 - 104262

ER -

The exosomes derived from CAR-T cell efficiently target mesothelin and reduce triple-negative breast cancer growth

Abstract

Funding

UN SDGs

Research Keywords

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