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Hematopoiesis-restricted minor histocompatibility antigens Ha-1- or Ha-2-specific T cells can induced complete remissions of relapsed leukemia.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 3/4/2003, Vol. 100 Issue 5, p2742. 6p. 1 Chart, 12 Graphs. - Publication Year :
- 2003
-
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-2positive 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[sup +] 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HEMATOPOIESIS
*DISEASE relapse
*LEUKEMIA
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 100
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 9345632
- Full Text :
- https://doi.org/10.1073/pnas.0530192100