Epitopes described in "Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia."

Article Authors:W A Erik Marijt; Mirjam H M Heemskerk; Freke M Kloosterboer; Els Goulmy; Michel G D Kester; Menno A W G van der Hoorn; Simone A P van Luxemburg-Heys; Manja Hoogeboom; Tuna Mutis; Jan Wouter Drijfhout; Jon J van Rood; Roel Willemze; J H Frederik Falkenburg
Article Title:Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia.
Reference Detail
Reference ID:1020287
Abstract:Donor lymphocyte infusion (DLI) into patients with a relapse of their leukemia or multiple myeloma after allogeneic stem cell transplantation (alloSCT) has been shown to be a successful treatment approach. The hematopoiesis-restricted minor histocompatibility antigens (mHAgs) HA-1 or HA-2 expressed on malignant cells of the recipient may serve as target antigens for alloreactive donor T cells. Recently we treated three mHAg HA-1- and/or HA-2-positive patients with a relapse of their disease after alloSCT with DLI from their mHAg HA-1- and/or HA-2-negative donors. Using HLA-A2HA-1 and HA-2 peptide tetrameric complexes we showed the emergence of HA-1- and HA-2-specific CD8(+) T cells in the blood of the recipients 5-7 weeks after DLI. The appearance of these tetramer-positive cells was followed immediately by a complete remission of the disease and restoration of 100% donor chimerism in each of the patients. Furthermore, cloned tetramer-positive T cells isolated during the clinical response specifically recognized HA-1 and HA-2 expressing malignant progenitor cells of the recipient and inhibited the growth of leukemic precursor cells in vitro. Thus, HA-1- and HA-2-specific cytotoxic T lymphocytes emerging in the blood of patients after DLI demonstrate graft-versus-leukemia or myeloma reactivity resulting in a durable remission. This finding implies that in vitro generated HA-1- and HA-2-specific cytotoxic T lymphocytes could be used as adoptive immunotherapy to treat hematological malignancies relapsing after alloSCT.
Affiliations:Department of Hematology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. w.a.f.marijt@lumc.nl.
Reference Type:Literature
PubMed ID:12601144
Journal:Proc Natl Acad Sci U S A
Journal Volume:100
Article Pages:2742-7
Journal ISSN:0027-8424
Article Chemical List:Antigens, CD8;Chromium Radioisotopes;Genetic Markers;HA-1 antigen;HA-2 antigen;Minor Histocompatibility Antigens;Neoplasm Proteins;Oligopeptides;Peptides;Fusion Proteins, bcr-abl
Article MeSH List:Antigens, CD8(biosynthesis); Bone Marrow Cells(cytology); CD8-Positive T-Lymphocytes(metabolism); Cell Division; Chromium Radioisotopes; Chromosomes, Human, X; Chromosomes, Human, Y; Female; Fusion Proteins, bcr-abl(metabolism); Genes, MHC Class I; Genetic Markers; Hematopoiesis; Humans; Immunotherapy(methods); In Situ Hybridization, Fluorescence; Leukemia(drug therapy; pathology); Male; Middle Aged; Minor Histocompatibility Antigens(pharmacology); Models, Genetic; Neoplasm Proteins(pharmacology); Oligopeptides(pharmacology); Peptides(chemistry); Phenotype; Recurrence; Remission Induction; Stem Cell Transplantation; Time Factors; Transplantation, Homologous
Curation Last Updated:2015-06-05 02:27:02