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Antigen receptor-redirected T cells derived from hematopoietic precursor cells lack expression of the endogenous TCR/CD3 receptor and exhibit specific antitumor capacities

Yasmine Van Caeneghem, Stijn De Munter (UGent) , Paola Tieppo (UGent) , Glenn Goetgeluk (UGent) , Karin Weening (UGent) , Greet Verstichel (UGent) , Sarah Bonte (UGent) , Tom Taghon (UGent) , Georges Leclercq (UGent) , Tessa Kerre (UGent) , et al.
(2017) ONCOIMMUNOLOGY. 6(3).
Author
Organization
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.
Keywords
Chimeric antigen receptor, cord blood, hematopoietic precursor cell, hematopoietic stem cell, immunotherapy, T cell, VERSUS-HOST-DISEASE, TCR GENE-THERAPY, B-CELL, CD28 COSTIMULATION, STEM-CELLS, LYMPHOCYTES, CHAINS, MATURE, TRANSPLANTATION, GENERATION

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Citation

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MLA
Van Caeneghem, Yasmine, Stijn De Munter, Paola Tieppo, et al. “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 (2017): n. pag. Print.
APA
Van Caeneghem, Y., De Munter, S., Tieppo, P., Goetgeluk, G., Weening, K., Verstichel, G., Bonte, S., et al. (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).
Chicago author-date
Van Caeneghem, Yasmine, Stijn De Munter, Paola Tieppo, Glenn Goetgeluk, Karin Weening, Greet Verstichel, Sarah Bonte, et al. 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).
Chicago author-date (all authors)
Van Caeneghem, Yasmine, Stijn De Munter, Paola Tieppo, Glenn Goetgeluk, Karin Weening, Greet Verstichel, Sarah Bonte, Tom Taghon, Georges Leclercq, Tessa Kerre, Reno Debets, David Vermijlen, Hinrich Abken, and Bart Vandekerckhove. 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).
Vancouver
1.
Van Caeneghem Y, De Munter S, Tieppo P, Goetgeluk G, Weening K, Verstichel G, et al. Antigen receptor-redirected T cells derived from hematopoietic precursor cells lack expression of the endogenous TCR/CD3 receptor and exhibit specific antitumor capacities. ONCOIMMUNOLOGY. 2017;6(3).
IEEE
[1]
Y. Van Caeneghem et al., “Antigen receptor-redirected T cells derived from hematopoietic precursor cells lack expression of the endogenous TCR/CD3 receptor and exhibit specific antitumor capacities,” ONCOIMMUNOLOGY, vol. 6, no. 3, 2017.
@article{8528442,
  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.},
  articleno    = {e1283460},
  author       = {Van Caeneghem, Yasmine and De Munter, Stijn and Tieppo, Paola and Goetgeluk, Glenn and Weening, Karin and Verstichel, Greet and Bonte, Sarah and Taghon, Tom and Leclercq, Georges and Kerre, Tessa and Debets, Reno and Vermijlen, David and Abken, Hinrich and Vandekerckhove, Bart},
  issn         = {2162-402X},
  journal      = {ONCOIMMUNOLOGY},
  keywords     = {Chimeric antigen receptor,cord blood,hematopoietic precursor cell,hematopoietic stem cell,immunotherapy,T cell,VERSUS-HOST-DISEASE,TCR GENE-THERAPY,B-CELL,CD28 COSTIMULATION,STEM-CELLS,LYMPHOCYTES,CHAINS,MATURE,TRANSPLANTATION,GENERATION},
  language     = {eng},
  number       = {3},
  pages        = {14},
  title        = {Antigen receptor-redirected T cells derived from hematopoietic precursor cells lack expression of the endogenous TCR/CD3 receptor and exhibit specific antitumor capacities},
  url          = {http://dx.doi.org/10.1080/2162402x.2017.1283460},
  volume       = {6},
  year         = {2017},
}

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