A novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells
Immunotherapy including chimeric antigen receptor (CAR) T cell therapy has revolutionized modern cancer therapy and has achieved remarkable remission and survival rates for several malignancies with historically dismal outcomes. The hinge of the CAR connects the antigen binding to the transmembrane...
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Elsevier
2021
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oai:doaj.org-article:00a59fbab47c466695dfcb76861adbf72021-12-02T05:02:12ZA novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells2372-770510.1016/j.omto.2021.11.003https://doaj.org/article/00a59fbab47c466695dfcb76861adbf72021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2372770521001522https://doaj.org/toc/2372-7705Immunotherapy including chimeric antigen receptor (CAR) T cell therapy has revolutionized modern cancer therapy and has achieved remarkable remission and survival rates for several malignancies with historically dismal outcomes. The hinge of the CAR connects the antigen binding to the transmembrane domain and can be exploited to confer features to CAR T cells including additional stimulation, targeted elimination or detection and enrichment of the genetically modified cells. For establishing a novel hinge derived from human CD34, we systematically tested CD34 fragments of different lengths, all containing the binding site of the QBend-10 monoclonal antibody, in a FMC63-based CD19 CAR lentiviral construct. A final construct of 99 amino acids called C6 proved to be the best candidate for flow cytometry-based detection of CAR T cells and >95% enrichment of genetically modified T cells on MACS columns. The C6 hinge was functionally indistinguishable from the commonly used CD8α hinge in vitro as well as in in vivo experiments in NSG mice. We also showed that the C6 hinge can be used for a variety of different CARs and mediates high killing efficacy without unspecific activation by target antigen-negative cells, thus making C6 ideally suited as a universal hinge for CARs for clinical applications.Arthur BisterTabea IbachCorinna HaistDenise SmorraKatharina RoelleckeMartin WagenmannKathrin ScheckenbachNorbert GattermannConstanze WiekHelmut HanenbergElsevierarticlechimeric antigen receptorCARhingeCD34detectionMACS enrichmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Therapy: Oncolytics, Vol 23, Iss , Pp 534-546 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
chimeric antigen receptor CAR hinge CD34 detection MACS enrichment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
chimeric antigen receptor CAR hinge CD34 detection MACS enrichment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Arthur Bister Tabea Ibach Corinna Haist Denise Smorra Katharina Roellecke Martin Wagenmann Kathrin Scheckenbach Norbert Gattermann Constanze Wiek Helmut Hanenberg A novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells |
| description |
Immunotherapy including chimeric antigen receptor (CAR) T cell therapy has revolutionized modern cancer therapy and has achieved remarkable remission and survival rates for several malignancies with historically dismal outcomes. The hinge of the CAR connects the antigen binding to the transmembrane domain and can be exploited to confer features to CAR T cells including additional stimulation, targeted elimination or detection and enrichment of the genetically modified cells. For establishing a novel hinge derived from human CD34, we systematically tested CD34 fragments of different lengths, all containing the binding site of the QBend-10 monoclonal antibody, in a FMC63-based CD19 CAR lentiviral construct. A final construct of 99 amino acids called C6 proved to be the best candidate for flow cytometry-based detection of CAR T cells and >95% enrichment of genetically modified T cells on MACS columns. The C6 hinge was functionally indistinguishable from the commonly used CD8α hinge in vitro as well as in in vivo experiments in NSG mice. We also showed that the C6 hinge can be used for a variety of different CARs and mediates high killing efficacy without unspecific activation by target antigen-negative cells, thus making C6 ideally suited as a universal hinge for CARs for clinical applications. |
| format |
article |
| author |
Arthur Bister Tabea Ibach Corinna Haist Denise Smorra Katharina Roellecke Martin Wagenmann Kathrin Scheckenbach Norbert Gattermann Constanze Wiek Helmut Hanenberg |
| author_facet |
Arthur Bister Tabea Ibach Corinna Haist Denise Smorra Katharina Roellecke Martin Wagenmann Kathrin Scheckenbach Norbert Gattermann Constanze Wiek Helmut Hanenberg |
| author_sort |
Arthur Bister |
| title |
A novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells |
| title_short |
A novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells |
| title_full |
A novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells |
| title_fullStr |
A novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells |
| title_full_unstemmed |
A novel CD34-derived hinge for rapid and efficient detection and enrichment of CAR T cells |
| title_sort |
novel cd34-derived hinge for rapid and efficient detection and enrichment of car t cells |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/00a59fbab47c466695dfcb76861adbf7 |
| work_keys_str_mv |
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