Donor-derived b2a2-specific T cells for immunotherapy of patients with chronic myeloid leukemia.
The BCR-ABL fusion proteins, b2a2 and b3a2, are potential targets for a beneficial graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation for chronic myeloid leukemia (CML). This study demonstrates that CD4+ T cells specific to the b2a2 peptide can be generated from a normal allogeneic stem cell transplant donor after stimulation with monocyte-derived dendritic cells (Mo-DC) using culture conditions applicable to clinical use. Stimulation of donor T-cell enriched mononuclear cells (MNC) with b2a2-pulsed Mo-DC produced approximately 3 x 10(9) b2a2-specific CD4+ T cells. The CD4+ T cells were HLA-DR7 restricted. These results confirm that the generation of donor derived b2a2-specific T cells for clinical use is feasible and warrants clinical testing after stem cell transplantation.
Crough
Tania
T
Department of Medicine, The University of Queensland, Brisbane, Australia.
Nieda
Mie
M
Morton
James
J
Bashford
John
J
Durrant
Simon
S
Nicol
Andrew J
AJ
D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005240:Feasibility Studies; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D020544:Graft vs Leukemia Effect; D015809:HLA-DR7 Antigen / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000628:therapy*; D017710:Lymphocyte Transfusion; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D036102:Peripheral Blood Stem Cell Transplantation; D014019:Tissue Donors; D014184:Transplantation, Homologous
D015809:HLA-DR7 Antigen; D015847:Interleukin-4; D007371:Interferon-gamma; D016044:Fusion Proteins, bcr-abl