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Single-cell cloning of human, donor-derived antileukemia T-cell lines for in vitro separation of graft-versus-leukemia effect from graft-versus-host reaction
- Publication Year :
- 2006
-
Abstract
- In previous studies, we showed the possibility of expanding in vitro polyclonal CTL lines directed against patient leukemia cells using effector cells derived from both HLA-matched and HLA-mismatched hematopoietic stem cell donors. Some CTL lines, especially those derived from an HLA-disparate donor, displayed residual alloreactivity against patient nonmalignant cells. In this study, we evaluated the possibility of separating in vitro CTLs with selective graft-versus-leukemia (GVL) activity from those potentially involved in the development of graft-versus-host disease (GVHD) through single T-cell cloning of antileukemia polyclonal CTL lines. We showed that CTLs that were expanded from a single T-cell clone (TCC), able to selectively kill leukemia blasts and devoid of alloreactivity towards nonmalignant cells, can be obtained from antileukemia alloreactive polyclonal CTL lines. TCCs expressed a wide repertoire of different T-cell receptor (TCR)-Vβ families, mainly produced IFNγ and interleukin 2, irrespective of CD8 or CD4 phenotype, and could be extensively expanded in vitro without losing their peculiar functional features. The feasibility of our approach for in vitro separation of GVL from GVH reaction opens perspectives for using TCCs, which are selectively reactive towards leukemia blasts, for antileukemia adoptive immune therapy approaches after hematopoietic stem cell transplantation, in particular from HLA-mismatched donors. (Cancer Res 2006; 66(14): 7310-6)
- Subjects :
- Adult
Male
Cancer Research
Adolescent
medicine.medical_treatment
T cell
Clone (cell biology)
chemical and pharmacologic phenomena
Graft vs Leukemia Effect
Hematopoietic stem cell transplantation
Biology
Graft vs Host Reaction
HLA Antigens
medicine
Cytotoxic T cell
Humans
Child
Hematopoietic Stem Cell Transplantation
Hematopoietic stem cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
medicine.disease
Clone Cells
CTL
Leukemia
medicine.anatomical_structure
Oncology
Leukemia, Myeloid
Child, Preschool
Immunology
Acute Disease
Cancer research
Female
CD8
T-Lymphocytes, Cytotoxic
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....06da9eeb1e1741f983553f9ab4850478