Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Van Caeneghem, Yasmine UNSPECIFIED UNSPECIFIED UNSPECIFIED De Munter, Stijn UNSPECIFIED orcid.org/0000-0003-3821-0620 UNSPECIFIED Tieppo, Paola UNSPECIFIED UNSPECIFIED UNSPECIFIED Goetgeluk, Glenn UNSPECIFIED UNSPECIFIED UNSPECIFIED Weening, Karin UNSPECIFIED UNSPECIFIED UNSPECIFIED Verstichel, Greet UNSPECIFIED UNSPECIFIED UNSPECIFIED Bonte, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Taghon, Tom UNSPECIFIED UNSPECIFIED UNSPECIFIED Leclercq, Georges UNSPECIFIED orcid.org/0000-0002-1691-5294 UNSPECIFIED Kerre, Tessa UNSPECIFIED UNSPECIFIED UNSPECIFIED Debets, Reno UNSPECIFIED UNSPECIFIED UNSPECIFIED Vermijlen, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Vandekerckhove, Bart UNSPECIFIED orcid.org/0000-0003-3828-4195 UNSPECIFIED
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:	Keywords Language VERSUS-HOST-DISEASE; TCR GENE-THERAPY; B-CELL; CD28 COSTIMULATION; STEM-CELLS; LYMPHOCYTES; CHAINS; MATURE; TRANSPLANTATION; GENERATION Multiple languages Oncology; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24670