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Antileukemic HLA-Restricted T-Cell Clones Generated With Naturally
Processed Peptides Eluted From Acute Myeloblastic Leukemia Blasts
Marina Ostankovitch,
Agnès Buzyn,
Delphine Bonhomme,
Francine Connan,
Didier Bouscary,
Fahrad Heshmati,
François Dreyfus,
Jeannine Choppin, and
Jean-Gérard Guillet
From the Institut Cochin de Génétique Moléculaire,
INSERM U445, Université René Descartes, Hôpital
Cochin; Service d'hématologie, Hôpital Cochin; and
Etablissement de transfusion sanguine, Hôpital Cochin, Paris,
France.
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.
Blood, Vol. 92 No. 1 (July 1), 1998:
pp. 19-24
© 1998 by The American Society of Hematology.
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