Journal
CELLULAR IMMUNOLOGY
Volume 360, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2020.104262
Keywords
CAR-T; Exosomes; Mesothelin; Triple-negative breast cancer; Tumor immunotherapy
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Funding
- National Natural Science Foundation of China [31900987]
- Heilongjiang Natural Science Foundation [YQ2019H022]
- Nantong Science and Technology Plan Project [JC2019146]
- Nantong University Clinical Medicine Project [2019JZ004]
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Exosomes derived from CAR-T cells targeting MSLN showed potential in inhibiting the growth of MSLN-positive triple-negative breast cancer cells, with characteristics similar to parental T cells. The expression of effector molecules may contribute to tumor killing, and in vivo studies demonstrated a highly effective tumor inhibition rate with no obvious side effects. The use of CAR-T cell exosomes has promising therapeutic potential against MSLN-expressing TNBC.
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.
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