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Chimeric antigen receptors containing the OX40 signalling domain enhance the persistence of T cells even under repeated stimulation with multiple myeloma target cells.
- Source :
-
Journal of Hematology & Oncology . 4/1/2022, Vol. 15 Issue 1, p1-6. 6p. - Publication Year :
- 2022
-
Abstract
- Persistence of CAR-T cell function is associated with relapse rate after CAR-T therapy, while co-stimulatory agents are highly concerned with the persistence of CAR-T cells. In this study, we designed and constructed a series of BCMA-targeting second-generation CAR constructs containing CD28, 41BB, and OX40 molecules, respectively, to identify the costimulatory domains most favorable for persistence. The results of routine in vitro studies showed that OX40-CAR-T and 41BB-CAR-T had similar antitumor effects and were superior to CD28-CAR-T in terms of proliferation and cytotoxicity. Although difficult to distinguish by conventional functional assays, OX40-CAR-T cells exhibited greater proliferation and enhanced immune memory than 41BB-CAR-T cells with the repeated stimulation assay by BCMA-expressing target cells. In vivo studies further demonstrated that OX40-CAR-T cells had stronger proliferative activity than 41BB-CAR-T cells, which was highly consistent with the in vitro antitumor activity and proliferation results. Our study provides for the first time a scientific basis for designing OX40-CAR-T cell therapy to improve relapse in patients with MM after CAR-T treatment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17568722
- Volume :
- 15
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Hematology & Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 156100804
- Full Text :
- https://doi.org/10.1186/s13045-022-01244-0