T-cells with a single tumor antigen-specific T-cell receptor can be generated
Acute myeloid leukemia (AML)
OP9-DL1
T-cell immunotherapy
hematopoietic stem cells
Journal
Oncoimmunology
ISSN: 2162-4011
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
2020
2020
Historique:
received:
19
08
2019
revised:
05
12
2019
accepted:
19
12
2019
entrez:
3
3
2020
pubmed:
3
3
2020
medline:
3
3
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32117593
doi: 10.1080/2162402X.2020.1727078
pii: 1727078
pmc: PMC7028335
doi:
Substances chimiques
Antigens, Neoplasm
0
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
1727078Informations de copyright
© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
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