Mesothelin-targeted CAR-NK Cells Derived From Induced Pluripotent Stem Cells Have a High Efficacy in Killing Triple-negative Breast Cancer Cells as Shown in Several Preclinical Models.

Autor:	Yang M; Department of Breast Cancer, Cancer Centre, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Shantou, Guangdong Province, China., Guan T; Guangdong Procapzoom Biosciences Inc., Guangzhou, Guangdong Province, China., Chen CF; The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, China., He LF; The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, China., Wu HM; The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, China., Zhang RD; The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, China., Li Y; Guangdong Procapzoom Biosciences Inc., Guangzhou, Guangdong Province, China., Lin YC; Guangdong Procapzoom Biosciences Inc., Guangzhou, Guangdong Province, China., Zeng H; Guangdong Procapzoom Biosciences Inc., Guangzhou, Guangdong Province, China., Wu JD; The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province, China.; Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Shantou, Guangdong Province, China.
Jazyk:	angličtina
Zdroj:	Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2023 Oct 01; Vol. 46 (8), pp. 285-294. Date of Electronic Publication: 2023 Aug 15.
DOI:	10.1097/CJI.0000000000000483
Abstrakt:	The emergence of immunotherapy has introduced a promising, novel approach to cancer treatment. While multiple chimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable clinical efficacy against leukemia, their effect on solid tumors has been limited. One potential option for treating solid tumors is the engineering of natural killer (NK) cells with CARs. Mesothelin (MSLN), a tumor differentiation antigen, is expressed on triple-negative breast cancer (TNBC) cells, making it a potential target for CAR-NK therapy in the treatment of TNBC. We first constructed induced pluripotent stem cells with stable anti-MSLN-CAR expression and subsequently differentiated these cells into mesothelin-targeted CAR-NK (MSLN-NK) cells. We then assessed the effects of MSLN-NK cells on TNBC cells both in vitro (using the MDA-MB-231 cell line), in vivo (in a CDX mouse model), and ex vivo (using patient-specific primary cells and patient-specific organoids), in which MSLN surface expression was confirmed. Our CDX study results indicated that MSLN-NK cells effectively killed MDA-MB-231 (MD231) cells in vitro, reduced tumor growth in the CDX mouse model of TNBC, and lysed patient-specific primary cells and patient-specific organoids derived from the tumor samples of TNBC patients. Our data demonstrated that MSLN-NK cells had high efficacy on killing TNBC cells in in vitro, in vivo, and ex vivo. Therefore, MSLN-NK could be a promising treatment option for TNBC patients. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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