Antileukemic HLA-restricted T-cell clones generated with naturally processed peptides eluted from acute myeloblastic leukemia blasts.
Recent studies have shown that transfusions of HLA-compatible donor lymphocytes may induce complete remission in marrow-grafted patients with relapses of acute myeloblastic leukemia (AML). We investigated the in vitro generation of antileukemia T-cell clones obtained from the peripheral blood mononuclear cells of a partially HLA-compatible donor (HLA-A2 and B7 molecules in common with the leukemic blasts) after stimulation with a pool of naturally processed peptides extracted from leukemic blast cells collected at diagnosis from a patient with hyperleucocytosis AML. We recovered a significant quantity of peptides that bound to the HLA-A2 or HLA-B7 molecules that were able to induce cytolytic T-lymphocyte (CTL) lines and clones specific for the eluted AML peptides and restricted to the HLA-A2 or B7 molecules. Such CTL line did not recognize the patient's nonleukemic cells, and one clone was able to interact with the leukemic blasts from which the naturally processed peptides had been eluted. Such T-cell clones might provide a rationale for the development of adoptive immunotherapy and could be used to improve the efficiency of HLA-compatible T-lymphocyte transfusions and the graft-versus-leukemia response in patients with AML.
Ostankovitch
M
M
Institut Cochin de Génétique Moléculaire, INSERM U445, France. ostankovitch@cochin.inser.fr
Buzyn
A
A
Bonhomme
D
D
Connan
F
F
Bouscary
D
D
Heshmati
F
F
Dreyfus
F
F
Choppin
J
J
Guillet
J G
JG
D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D015793:HLA-B7 Antigen / Q000276:immunology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D015793:HLA-B7 Antigen; D010455:Peptides