T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources
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, mar...
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doaj-8a9e6e8dd9154340bb2f53f8c0e0027b2021-09-24T14:41:23ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2020.17270781727078T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sourcesSarah Bonte0Stijn De Munter1Glenn Goetgeluk2Joline Ingels3Melissa Pille4Lore Billiet5Tom Taghon6Georges Leclercq7Bart Vandekerckhove8Tessa Kerre9Ghent UniversityCancer Research Institute Ghent (CRIG)Ghent UniversityGhent UniversityGhent UniversityGhent UniversityCancer Research Institute Ghent (CRIG)Cancer Research Institute Ghent (CRIG)Cancer Research Institute Ghent (CRIG)Ghent UniversityChimeric 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.http://dx.doi.org/10.1080/2162402X.2020.1727078acute myeloid leukemia (aml)t-cell immunotherapyhematopoietic stem cellsop9-dl1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sarah Bonte Stijn De Munter Glenn Goetgeluk Joline Ingels Melissa Pille Lore Billiet Tom Taghon Georges Leclercq Bart Vandekerckhove Tessa Kerre |
spellingShingle |
Sarah Bonte Stijn De Munter Glenn Goetgeluk Joline Ingels Melissa Pille Lore Billiet Tom Taghon Georges Leclercq Bart Vandekerckhove Tessa Kerre T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources OncoImmunology acute myeloid leukemia (aml) t-cell immunotherapy hematopoietic stem cells op9-dl1 |
author_facet |
Sarah Bonte Stijn De Munter Glenn Goetgeluk Joline Ingels Melissa Pille Lore Billiet Tom Taghon Georges Leclercq Bart Vandekerckhove Tessa Kerre |
author_sort |
Sarah Bonte |
title |
T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources |
title_short |
T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources |
title_full |
T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources |
title_fullStr |
T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources |
title_full_unstemmed |
T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources |
title_sort |
t-cells with a single tumor antigen-specific t-cell receptor can be generated in vitro from clinically relevant stem cell sources |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2020-01-01 |
description |
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. |
topic |
acute myeloid leukemia (aml) t-cell immunotherapy hematopoietic stem cells op9-dl1 |
url |
http://dx.doi.org/10.1080/2162402X.2020.1727078 |
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