Document Detail


Generation of potent antitumor CTL from patients with multiple myeloma directed against HM1.24.
MedLine Citation:
PMID:  15867238     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The purpose of this work was to test the suitability of the HM1.24 antigen as a CTL target for immunotherapy of patients with multiple myeloma. EXPERIMENTAL DESIGN: Antigen-specific T cells were generated from patients with multiple myeloma using stimulation with protein-pulsed dendritic cells and tested in ELISPOT and CTL assays. RESULTS: HM1.24-primed T cells responded selectively to HM1.24-loaded autologous peripheral blood mononuclear cells (PBMC) in an IFN-gamma ELISPOT assay (median, 342; range, 198-495 IFN-gamma-producing cells/10(5) cf. unloaded PBMC median, 98; range, 7-137; P < 0.05, n = 5) and also to autologous malignant plasma cells (MPC; median, 227; range, 153-335; P < 0.05 when compared with the response to allogeneic MPC median, 57; range, 22-158; n = 5). HM1.24-primed T cells lysed autologous MPC (at 20:1 E/T ratio: median, 48% specific killing; range, 23-88%; at 10:1 E/T ratio: median, 43%; range, 15-80%; n = 12) but not allogeneic MPC. Lysis of autologous MPC was inhibited by anti-MHC class I but not anti-MHC class II antibodies and was blocked by Concanamycin A. Lysis of autologous MPC was blocked by competition with autologous HM1.24-transfected dendritic cells (10:1 ratio with autologous MPC). Unmanipulated, or control plasmid-transfected dendritic cells had no effect on lysis of autologous MPC. CONCLUSION: Our results indicate that HM1.24 is a promising target for immunotherapy of multiple myeloma.
Authors:
Steven B Rew; Karl Peggs; Irene Sanjuan; Arnold R Pizzey; Yasuo Koishihara; Shigeto Kawai; Masaaki Kosaka; Shuji Ozaki; Benjamin Chain; Kwee L Yong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  11     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-05-03     Completed Date:  2005-08-01     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3377-84     Citation Subset:  IM    
Affiliation:
Department of Haematology, Royal Free and University College Medical School, London, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD
Antigens, CD45 / immunology
CD4-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / immunology
Cell Line, Tumor
Cytotoxicity Tests, Immunologic
Cytotoxicity, Immunologic / immunology
Dendritic Cells / immunology,  metabolism
Flow Cytometry / methods
Humans
Immunophenotyping
Interferon-gamma / secretion
Membrane Glycoproteins / genetics,  immunology*,  physiology
Multiple Myeloma / immunology*,  pathology
Perforin
Plasma Cells / immunology
Pore Forming Cytotoxic Proteins
Signal Transduction / immunology
T-Lymphocytes / immunology,  metabolism
T-Lymphocytes, Cytotoxic / immunology*
Transfection
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/BST2 protein, human; 0/Membrane Glycoproteins; 0/Pore Forming Cytotoxic Proteins; 126465-35-8/Perforin; 82115-62-6/Interferon-gamma; EC 3.1.3.48/Antigens, CD45

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