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-ompatible donor lym phocytes 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 peri pheral blood mononuclear cells of a partially HLA-ompatible donor (HLA -A2 and B7 molecules in common with the leukemic blasts) after stimula tion with a pool of naturally processed peptides extracted from leukem ic blast cells collected at diagnosis from a patient with hyperleucocy tosis AML. We recovered a significant quantity of peptides that bound to the HLA-AS or HLA-B7 molecules that were able to induce cytolytic T -lymphocyte (CTL) lines and clones specific for the eluted AML peptide s 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 i nteract with the leukemic blasts from which the naturally processed pe ptides had been eluted. Such T-cell clones might provide a rationale f or the development of adoptive immunotherapy and could be used to impr ove the efficiency of HLA-compatible T-lymphocyte transfusions and the graft-versus-leukemia response in patients with AML. (C) 1998 by The American Society of Hematology.