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Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure.
- Source :
- OncoImmunology; 2022, Vol. 11 Issue 1, p1-13, 13p
- Publication Year :
- 2022
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 21624011
- Volume :
- 11
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- OncoImmunology
- Publication Type :
- Academic Journal
- Accession number :
- 161372696
- Full Text :
- https://doi.org/10.1080/2162402X.2022.2033528