Back to Search
Start Over
A novel chimeric antigen receptor redirecting T-cell specificity towards CD26 + cancer cells.
- Source :
-
Leukemia [Leukemia] 2021 Jan; Vol. 35 (1), pp. 119-129. Date of Electronic Publication: 2020 Apr 21. - Publication Year :
- 2021
-
Abstract
- Chimeric antigen receptor (CAR) T-cell immunotherapy is rapidly emerging as a promising novel treatment for malignancies. To broaden the success of CAR T-cell treatment for chronic myeloid leukaemia (CML), we attempted to construct a CD26 CAR T-cell product to target tyrosine kinase inhibitor-insensitive leukaemia stem cells (LSCs), which have been a challenge to cure for several decades and can be discriminated from healthy stem cells by the robust biomarker CD26. Of additional interest is that CD26 has also been reported to be a multi-purpose therapeutic target for other malignancies. Here, we constructed CD26 CAR T cells utilizing lentiviral transduction methods and verified them by flow cytometry analysis and RNA-seq. We found that the initial expansion of CD26 CAR-transduced T cells was delayed due to transient fratricide, but subsequent expansion was accelerated. CD26 CAR T cells exhibited cytotoxicity against the CD26 <superscript>+</superscript> T-cell lymphoma cell line Karpas 299, CD26-overexpressing K562 cells and primary CML LSCs, activated multiple effector functions in co-culture assays, and limited tumour progression in a mouse model; but there was some off-tumour cytotoxicity towards activated lymphocytes. In conclusion, these results establish the feasibility of using CD26 as an antigen for CAR T cells targeting CD26 <superscript>+</superscript> tumour cells.
- Subjects :
- Animals
Biomarkers
Cell Line, Tumor
Cytotoxicity, Immunologic
Disease Models, Animal
Gene Expression Profiling
Humans
Immunophenotyping
Mice
Neoplasms immunology
Neoplasms therapy
Receptors, Antigen, T-Cell genetics
Receptors, Chimeric Antigen genetics
T-Cell Antigen Receptor Specificity genetics
Xenograft Model Antitumor Assays
Dipeptidyl Peptidase 4 immunology
Immunotherapy, Adoptive adverse effects
Immunotherapy, Adoptive methods
Receptors, Antigen, T-Cell immunology
Receptors, Chimeric Antigen immunology
T-Cell Antigen Receptor Specificity immunology
T-Lymphocytes immunology
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5551
- Volume :
- 35
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Leukemia
- Publication Type :
- Academic Journal
- Accession number :
- 32317776
- Full Text :
- https://doi.org/10.1038/s41375-020-0824-y