Abstract |
We previously showed that a peptide (PR1) derived from the primary granule enzyme proteinase 3 induced peptide specific cytotoxic T lymphocytes (CTL) in a normal HLA-A2.1+ individual. These CTL showed HLA-restricted cytotoxicity to myeloid leukemias (which overexpress proteinase 3). To further investigate their antileukemic potential, we studied the ability of PR1-specific CTL, derived from two HLA-A2.1+ normal individuals, to inhibit colony-forming unit granulocyte-macrophage (CFU-GM) from normal and leukemic individuals. CTL from 20 day PR1 peptide-pulsed lymphocyte cultures showed 89% to 98% HLA-A2.1-restricted colony inhibition of chronic myeloid leukemia targets. Colony formation in normal HLA-A2.1+ bone marrow or HLA-A2.1- CML cells was not inhibited. Sequencing of the exon encoding PR1 showed that colony inhibition was not caused by polymorphic differences in proteinase 3 between effectors and targets. Analysis by flow cytometry showed that proteinase 3 was overexpressed in the leukemia targets compared with normal marrow targets (median channel fluorescence 1,399 v 298, P = .009). These results show that PR1-specific allogeneic T cells preferentially inhibit leukemic CFU-GM based on overexpression of proteinase 3, and that proteinase 3-specific CTL could be used for leukemia-specific adoptive immunotherapy.
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Authors | J J Molldrem, E Clave, Y Z Jiang, D Mavroudis, A Raptis, N Hensel, V Agarwala, A J Barrett |
Journal | Blood
(Blood)
Vol. 90
Issue 7
Pg. 2529-34
(Oct 01 1997)
ISSN: 0006-4971 [Print] United States |
PMID | 9326217
(Publication Type: Journal Article)
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Chemical References |
- HLA-A2 Antigen
- Neoplasm Proteins
- Peptide Fragments
- Serine Endopeptidases
- Myeloblastin
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Topics |
- Bone Marrow
(pathology)
- Cells, Cultured
- Cytotoxicity, Immunologic
- Exons
(genetics)
- HLA-A2 Antigen
(immunology)
- Humans
- Immunotherapy, Adoptive
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
(immunology, pathology)
- Myeloblastin
- Neoplasm Proteins
(chemistry, genetics, immunology)
- Neoplastic Stem Cells
(enzymology, immunology)
- Peptide Fragments
(genetics, immunology)
- Serine Endopeptidases
(chemistry, genetics, immunology)
- T-Lymphocytes, Cytotoxic
(immunology)
- Tumor Cells, Cultured
- Tumor Stem Cell Assay
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