Van Caeneghem, Yasmine, De Munter, Stijn ORCID: 0000-0003-3821-0620, Tieppo, Paola, Goetgeluk, Glenn, Weening, Karin, Verstichel, Greet, Bonte, Sarah, Taghon, Tom, Leclercq, Georges ORCID: 0000-0002-1691-5294, Kerre, Tessa, Debets, Reno, Vermijlen, David, Abken, Hinrich and Vandekerckhove, Bart ORCID: 0000-0003-3828-4195 (2017). Antigen receptor-redirected T cells derived from hematopoietic precursor cells lack expression of the endogenous TCR/CD3 receptor and exhibit specific antitumor capacities. OncoImmunology, 6 (3). PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 2162-402X

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Abstract

Recent clinical studies indicate that adoptive T-cell therapy and especially chimeric antigen receptor (CAR) T-cell therapy is a very potent and potentially curative treatment for B-lineage hematologic malignancies. Currently, autologous peripheral blood T cells are used for adoptive T-cell therapy. Adoptive T cells derived from healthy allogeneic donors may have several advantages; however, the expected occurrence of graft versus host disease (GvHD) as a consequence of the diverse allogeneic T-cell receptor (TCR) repertoire expressed by these cells compromises this approach. Here, we generated T cells from cord blood hematopoietic progenitor cells (HPCs) that were transduced to express an antigen receptor (AR): either a CAR or a TCR with or without built-in CD28 co-stimulatory domains. These AR-transgenic HPCs were culture-expanded on an OP9-DL1 feeder layer and subsequently differentiated to CD5(+)CD7(+) T-lineage precursors, to CD4(+) CD8(+) double positive cells and finally to mature AR(+) T cells. The AR(+) T cells were largely naive CD45RA(+)CD62L(+) T cells. These T cells had mostly germline TCR alpha and TCR beta loci and therefore lacked surface-expressed CD3/TCR alpha beta complexes. The CD3(-) AR-transgenic cells were mono-specific, functional T cells as they displayed specific cytotoxic activity. Cytokine production, including IL-2, was prominent in those cells bearing ARs with built-in CD28 domains. Data sustain the concept that cord blood HPC derived, in vitro generated allogeneic CD3(-) AR(+) T cells can be used to more effectively eliminate malignant cells, while at the same time limiting the occurrence of GvHD.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Van Caeneghem, YasmineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Munter, StijnUNSPECIFIEDorcid.org/0000-0003-3821-0620UNSPECIFIED
Tieppo, PaolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goetgeluk, GlennUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weening, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Verstichel, GreetUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bonte, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taghon, TomUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leclercq, GeorgesUNSPECIFIEDorcid.org/0000-0002-1691-5294UNSPECIFIED
Kerre, TessaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Debets, RenoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vermijlen, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abken, HinrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vandekerckhove, BartUNSPECIFIEDorcid.org/0000-0003-3828-4195UNSPECIFIED
URN: urn:nbn:de:hbz:38-246706
DOI: 10.1080/2162402X.2017.1283460
Journal or Publication Title: OncoImmunology
Volume: 6
Number: 3
Date: 2017
Publisher: TAYLOR & FRANCIS INC
Place of Publication: PHILADELPHIA
ISSN: 2162-402X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
VERSUS-HOST-DISEASE; TCR GENE-THERAPY; B-CELL; CD28 COSTIMULATION; STEM-CELLS; LYMPHOCYTES; CHAINS; MATURE; TRANSPLANTATION; GENERATIONMultiple languages
Oncology; ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/24670

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