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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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-A2/HA-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 malignances relapsing after alloSCT.

Original languageEnglish
Pages (from-to)2742-2747
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number5
DOIs
Publication statusPublished - 4 Mar 2003
Externally publishedYes

Cite this

Marijt, W. A. E., Heemskerk, M. H. M., Kloosterboer, F. M., Goulmy, E., Kester, M. G. D., Van der Hoorn, M. A. W. G., ... Falkenburg, J. H. F. (2003). Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia. Proceedings of the National Academy of Sciences of the United States of America, 100(5), 2742-2747. https://doi.org/10.1073/pnas.0530192100