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T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources

Sarah Bonte (UGent) , Stijn De Munter (UGent) , Glenn Goetgeluk (UGent) , Joline Ingels (UGent) , Melissa Pille (UGent) , Lore Billiet (UGent) , Tom Taghon (UGent) , Georges Leclercq (UGent) , Bart Vandekerckhove (UGent) and Tessa Kerre (UGent)
(2020) ONCOIMMUNOLOGY. 9(1).
Author
Organization
Abstract
Chimeric antigen receptor (CAR) T-cells have shown great promise in the treatment of B-cell malignancies. For acute myeloid leukemia (AML), however, the optimal target surface antigen has yet to be discovered. Alternatively, T-cell receptor (TCR)-redirected T-cells target intracellular antigens, marking a broader territory of available target antigens. Currently, adoptive TCR T-cell therapy uses peripheral blood lymphocytes for the introduction of a transgenic TCR. However, this can cause graft-versus-host disease, due to mispairing of introduced and endogenous TCR chains. Therefore, we started from hematopoietic stem and progenitor cells (HSPC), that do not express a TCR yet, isolated from healthy donors, patients in remission after chemotherapy and AML patients at diagnosis. Using the OP9-DL1 in vitro co-culture system and agonist selection, TCR-transduced HSPC develop into mature tumor antigen-specific T-cells with only one TCR. We show here that this approach is feasible with adult HSPC from clinically relevant sources, albeit with slower maturation and lower cell yield compared to cord blood HSPC. Moreover, cryopreservation of HSPC does not have an effect on cell numbers or functionality of the generated T-cells. In conclusion, we show here that it is feasible to generate TA-specific T-cells from HSPC from adult healthy donors and patients and we believe these T-cells could be of use as a very valuable form of patient-tailored T-cell immunotherapy.
Keywords
Immunology, Immunology and Allergy, Oncology, Acute myeloid leukemia (AML), T-cell immunotherapy, hematopoietic stem cells, OP9-DL1, ACUTE MYELOID-LEUKEMIA, TERM-FOLLOW-UP, PROGENITOR CELLS, B-CELL, CD8(+), EXPRESSION, RELAPSE, ACTIVATION, EVOLUTION, SUBSET

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MLA
Bonte, Sarah, et al. “T-Cells with a Single Tumor Antigen-Specific T-Cell Receptor Can Be Generated in Vitro from Clinically Relevant Stem Cell Sources.” ONCOIMMUNOLOGY, vol. 9, no. 1, 2020, doi:10.1080/2162402x.2020.1727078.
APA
Bonte, S., De Munter, S., Goetgeluk, G., Ingels, J., Pille, M., Billiet, L., … Kerre, T. (2020). T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources. ONCOIMMUNOLOGY, 9(1). https://doi.org/10.1080/2162402x.2020.1727078
Chicago author-date
Bonte, Sarah, Stijn De Munter, Glenn Goetgeluk, Joline Ingels, Melissa Pille, Lore Billiet, Tom Taghon, Georges Leclercq, Bart Vandekerckhove, and Tessa Kerre. 2020. “T-Cells with a Single Tumor Antigen-Specific T-Cell Receptor Can Be Generated in Vitro from Clinically Relevant Stem Cell Sources.” ONCOIMMUNOLOGY 9 (1). https://doi.org/10.1080/2162402x.2020.1727078.
Chicago author-date (all authors)
Bonte, Sarah, Stijn De Munter, Glenn Goetgeluk, Joline Ingels, Melissa Pille, Lore Billiet, Tom Taghon, Georges Leclercq, Bart Vandekerckhove, and Tessa Kerre. 2020. “T-Cells with a Single Tumor Antigen-Specific T-Cell Receptor Can Be Generated in Vitro from Clinically Relevant Stem Cell Sources.” ONCOIMMUNOLOGY 9 (1). doi:10.1080/2162402x.2020.1727078.
Vancouver
1.
Bonte S, De Munter S, Goetgeluk G, Ingels J, Pille M, Billiet L, et al. T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources. ONCOIMMUNOLOGY. 2020;9(1).
IEEE
[1]
S. Bonte et al., “T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources,” ONCOIMMUNOLOGY, vol. 9, no. 1, 2020.
@article{8663525,
  abstract     = {{Chimeric antigen receptor (CAR) T-cells have shown great promise in the treatment of B-cell malignancies. For acute myeloid leukemia (AML), however, the optimal target surface antigen has yet to be discovered. Alternatively, T-cell receptor (TCR)-redirected T-cells target intracellular antigens, marking a broader territory of available target antigens. Currently, adoptive TCR T-cell therapy uses peripheral blood lymphocytes for the introduction of a transgenic TCR. However, this can cause graft-versus-host disease, due to mispairing of introduced and endogenous TCR chains. Therefore, we started from hematopoietic stem and progenitor cells (HSPC), that do not express a TCR yet, isolated from healthy donors, patients in remission after chemotherapy and AML patients at diagnosis. Using the OP9-DL1 in vitro co-culture system and agonist selection, TCR-transduced HSPC develop into mature tumor antigen-specific T-cells with only one TCR. We show here that this approach is feasible with adult HSPC from clinically relevant sources, albeit with slower maturation and lower cell yield compared to cord blood HSPC. Moreover, cryopreservation of HSPC does not have an effect on cell numbers or functionality of the generated T-cells. In conclusion, we show here that it is feasible to generate TA-specific T-cells from HSPC from adult healthy donors and patients and we believe these T-cells could be of use as a very valuable form of patient-tailored T-cell immunotherapy.}},
  articleno    = {{e1727078}},
  author       = {{Bonte, Sarah and De Munter, Stijn and Goetgeluk, Glenn and Ingels, Joline and Pille, Melissa and Billiet, Lore and Taghon, Tom and Leclercq, Georges and Vandekerckhove, Bart and Kerre, Tessa}},
  issn         = {{2162-402X}},
  journal      = {{ONCOIMMUNOLOGY}},
  keywords     = {{Immunology,Immunology and Allergy,Oncology,Acute myeloid leukemia (AML),T-cell immunotherapy,hematopoietic stem cells,OP9-DL1,ACUTE MYELOID-LEUKEMIA,TERM-FOLLOW-UP,PROGENITOR CELLS,B-CELL,CD8(+),EXPRESSION,RELAPSE,ACTIVATION,EVOLUTION,SUBSET}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{12}},
  title        = {{T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources}},
  url          = {{http://dx.doi.org/10.1080/2162402x.2020.1727078}},
  volume       = {{9}},
  year         = {{2020}},
}

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