Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure.

Chimeric antigen receptor (CAR) T cell therapies have resulted in profound clinical responses in the treatment of CD19-positive hematological malignancies, but a significant proportion of patients do not respond or relapse eventually. As an alternative to CAR T cells, T cells can be engineered to express a tumor-targeting T cell receptor (TCR). Due to HLA restriction of TCRs, CARs have emerged as a preferred treatment moiety when targeting surface antigens, despite the fact that functional differences between engineered TCR (eTCR) T and CAR T cells remain ill-defined. Here, we compared the activity of CAR T cells versus engineered TCR T cells in targeting the B cell malignancy-associated antigen CD20 as a function of antigen exposure. We found CAR T cells to be more potent effector cells, producing higher levels of cytokines and killing more efficiently than eTCR T cells in a short time frame. However, we revealed that the increase of antigen exposure significantly impaired CAR T cell expansion, a phenotype defined by high expression of coinhibitory molecules and effector differentiation. In contrast, eTCR T cells expanded better than CAR T cells under high antigenic pressure, with lower expression of coinhibitory molecules and maintenance of an early differentiation phenotype, and comparable clearance of tumor cells. © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

Citation

Tassilo L A Wachsmann, Anne K Wouters, Dennis F G Remst, Renate S Hagedoorn, Miranda H Meeuwsen, Eline van Diest, Jeanette Leusen, Jürgen Kuball, J H Frederik Falkenburg, Mirjam H M Heemskerk. Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure. Oncoimmunology. 2022;11(1):2033528

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PMID: 35127255

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