Generation of donor-derived Wilms tumor antigen 1-specific cytotoxic T lymphocytes with potent anti-leukemia activity for somatic cell therapy in children given haploidentical stem cell transplantation : a feasibility pre-clinical study
Copyright © 2019. Published by Elsevier Inc..
BACKGROUND: The Wilms tumor antigen 1 (WT1) is over-expressed in a vast majority of adult and childhood acute leukemia and myelodysplastic syndromes, being lowly or transiently expressed in normal tissues and hematopoietic stem cells (HSCs). A number of HLA-restricted WT1 epitopes are immunogenic, allowing the in vitro induction of WT1-specific cytotoxic T lymphocytes (CTLs) from patients and healthy donors.
AIM: The aim of the study was to investigate the feasibility of producing WT1-specific CTLs suitable for somatic cell therapy to prevent or treat relapse in children with acute myeloid or lymphoblastic leukemia given haploidentical HSC transplantation (haplo-HSCT).
METHODS: For WT1-specific CTL production, donor-derived either peripheral blood mononuclear cells (PBMCs) or CD8+ lymphocytes were stimulated with WT1 peptide-loaded donor dendritic cells in the presence of interleukin (IL)-7 and IL-12. Effector cells were re-stimulated once with irradiated donor PBMCs pulsed with WT1-peptides, and then expanded in an antigen-independent way.
RESULTS: WT1-specific CTLs, displaying high-level cytotoxicity against patients' leukemia blasts and negligible activity against patients' non-malignant cells, were obtained from both PBMCs and CD8+ lymphocytes. WT1-specific CTLs obtained from PBMCs showed a better expansion capacity and better anti-leukemia activity than those obtained from CD8+ lymphocytes, even though the difference was not statistically significant. In CTLs derived from PBMCs, both CD8+ and CD4+ subpopulations displayed strong anti-leukemia cytotoxic activity.
DISCUSSION: Results of this pre-clinical study pave the way to a somatic cell therapy approach aimed at preventing or treating relapse in children given haplo-HSCT for WT1-positive leukemia.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Cytotherapy - 21(2019), 9 vom: 26. Sept., Seite 958-972 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ferulli, Federica [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.05.2020 Date Revised 06.05.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jcyt.2019.06.007 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM298931427 |
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| 245 | 1 | 0 | |a Generation of donor-derived Wilms tumor antigen 1-specific cytotoxic T lymphocytes with potent anti-leukemia activity for somatic cell therapy in children given haploidentical stem cell transplantation |b a feasibility pre-clinical study |
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| 500 | |a Date Revised 06.05.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019. Published by Elsevier Inc. | ||
| 520 | |a BACKGROUND: The Wilms tumor antigen 1 (WT1) is over-expressed in a vast majority of adult and childhood acute leukemia and myelodysplastic syndromes, being lowly or transiently expressed in normal tissues and hematopoietic stem cells (HSCs). A number of HLA-restricted WT1 epitopes are immunogenic, allowing the in vitro induction of WT1-specific cytotoxic T lymphocytes (CTLs) from patients and healthy donors | ||
| 520 | |a AIM: The aim of the study was to investigate the feasibility of producing WT1-specific CTLs suitable for somatic cell therapy to prevent or treat relapse in children with acute myeloid or lymphoblastic leukemia given haploidentical HSC transplantation (haplo-HSCT) | ||
| 520 | |a METHODS: For WT1-specific CTL production, donor-derived either peripheral blood mononuclear cells (PBMCs) or CD8+ lymphocytes were stimulated with WT1 peptide-loaded donor dendritic cells in the presence of interleukin (IL)-7 and IL-12. Effector cells were re-stimulated once with irradiated donor PBMCs pulsed with WT1-peptides, and then expanded in an antigen-independent way | ||
| 520 | |a RESULTS: WT1-specific CTLs, displaying high-level cytotoxicity against patients' leukemia blasts and negligible activity against patients' non-malignant cells, were obtained from both PBMCs and CD8+ lymphocytes. WT1-specific CTLs obtained from PBMCs showed a better expansion capacity and better anti-leukemia activity than those obtained from CD8+ lymphocytes, even though the difference was not statistically significant. In CTLs derived from PBMCs, both CD8+ and CD4+ subpopulations displayed strong anti-leukemia cytotoxic activity | ||
| 520 | |a DISCUSSION: Results of this pre-clinical study pave the way to a somatic cell therapy approach aimed at preventing or treating relapse in children given haplo-HSCT for WT1-positive leukemia | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Wilms tumor antigen 1 | |
| 650 | 4 | |a acute leukemia | |
| 650 | 4 | |a allogeneic hematopoietic stem cell transplantation | |
| 650 | 4 | |a anti-tumor immunotherapy | |
| 650 | 4 | |a cytotoxic T lymphocytes | |
| 650 | 4 | |a somatic cell therapy | |
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| 650 | 7 | |a Interferon-gamma |2 NLM | |
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| 700 | 1 | |a Zecca, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Montagna, Daniela |e verfasserin |4 aut | |
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