Cytotoxic T lymphocytes specific for a nonpolymorphic proteinase 3 peptide preferentially inhibit chronic myeloid leukemia colony-forming units

Jeffrey J Molldrem, Emmanuel Clave, Yin Zheng Jiang, Dimitrios Mavroudis, Anastasios Raptis, Nancy Hensel, Vaishali Agarwala, A. John Barrett

Research output: Contribution to journalArticle

205 Citations (Scopus)

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 HLAA2.1+ 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.

Original languageEnglish (US)
Pages (from-to)2529-2534
Number of pages6
JournalBlood
Volume90
Issue number7
StatePublished - Oct 1 1997

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Myeloblastin
T-cells
Cytotoxic T-Lymphocytes
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Stem Cells
Peptides
Granulocyte-Macrophage Progenitor Cells
Macrophages
Leukemia
Bone Marrow
Adoptive Immunotherapy
Emitter coupled logic circuits
Myeloid Leukemia
Lymphocytes
Flow cytometry
Cytotoxicity
Cell culture
Exons
Flow Cytometry
Bone

ASJC Scopus subject areas

  • Hematology

Cite this

Molldrem, J. J., Clave, E., Jiang, Y. Z., Mavroudis, D., Raptis, A., Hensel, N., ... Barrett, A. J. (1997). Cytotoxic T lymphocytes specific for a nonpolymorphic proteinase 3 peptide preferentially inhibit chronic myeloid leukemia colony-forming units. Blood, 90(7), 2529-2534.

Cytotoxic T lymphocytes specific for a nonpolymorphic proteinase 3 peptide preferentially inhibit chronic myeloid leukemia colony-forming units. / Molldrem, Jeffrey J; Clave, Emmanuel; Jiang, Yin Zheng; Mavroudis, Dimitrios; Raptis, Anastasios; Hensel, Nancy; Agarwala, Vaishali; Barrett, A. John.

In: Blood, Vol. 90, No. 7, 01.10.1997, p. 2529-2534.

Research output: Contribution to journalArticle

Molldrem, JJ, Clave, E, Jiang, YZ, Mavroudis, D, Raptis, A, Hensel, N, Agarwala, V & Barrett, AJ 1997, 'Cytotoxic T lymphocytes specific for a nonpolymorphic proteinase 3 peptide preferentially inhibit chronic myeloid leukemia colony-forming units', Blood, vol. 90, no. 7, pp. 2529-2534.
Molldrem, Jeffrey J ; Clave, Emmanuel ; Jiang, Yin Zheng ; Mavroudis, Dimitrios ; Raptis, Anastasios ; Hensel, Nancy ; Agarwala, Vaishali ; Barrett, A. John. / Cytotoxic T lymphocytes specific for a nonpolymorphic proteinase 3 peptide preferentially inhibit chronic myeloid leukemia colony-forming units. In: Blood. 1997 ; Vol. 90, No. 7. pp. 2529-2534.
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