2022
DOI: 10.1080/2162402x.2022.2093426
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Trogocytosis and fratricide killing impede MSLN-directed CAR T cell functionality

Abstract: Successful translation of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors has proved to be troublesome, mainly due to the complex tumor microenvironment promoting T cell dysfunction and antigen heterogeneity. Mesothelin (MSLN) has emerged as an attractive target for CAR T cell therapy of several solid malignancies, including ovarian cancer. To improve clinical response rates with MSLN-CAR T cells, a better understanding of the mechanisms impacting CAR T cell functionality … Show more

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Cited by 18 publications
(22 citation statements)
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“… 27 45 In line with previous data, trogocytic CAR T cells displayed a T EM profile with higher expression levels of PD-1, LAG-3 and TIM-3, as well as CD56 and FASL, indicative of both activation and exhaustion. 45 46 The low frequency of trogocytic M1xx CAR T cells observed in our two models suggest that superior tumor control as seen with M1xx CAR T cells correlates to lower trogocytic activity.…”
Section: Discussionmentioning
confidence: 70%
“… 27 45 In line with previous data, trogocytic CAR T cells displayed a T EM profile with higher expression levels of PD-1, LAG-3 and TIM-3, as well as CD56 and FASL, indicative of both activation and exhaustion. 45 46 The low frequency of trogocytic M1xx CAR T cells observed in our two models suggest that superior tumor control as seen with M1xx CAR T cells correlates to lower trogocytic activity.…”
Section: Discussionmentioning
confidence: 70%
“…Overexpression of MSLN can be detected in CRC ( 30 ). MSLN is an important CAR-T cells target in solid tumors ( 31 , 32 ). In a recent study, the efficacy of MSLN-CAR-T cells on colon cancer xenografts was investigated.…”
Section: Basic Experimental Of Car-t Cells Therapy For Crcmentioning
confidence: 99%
“…Trogocytosis is a rapid process of cellular interaction that occurs in immunotherapy [ 17 , 18 ]. Immune cells, including T cells and natural killer (NK) cells, physically nibble off a portion of the tumor cell membrane at the stage of identifying the tumor cell, transferring antigens from the cell membrane of the target cell to the surface of the immune cell [ 19 , 20 ]. After the antigen is transferred to immune cells that do not express the antigen themselves, it can lead to mutual killing of immune cells, inhibit the effectiveness of immunotherapy, and promote tumor growth and metastasis [ 21 , 22 ].…”
Section: Introductionmentioning
confidence: 99%