Generation of Potent Antitumor CTL from Patients with Multiple Myeloma Directed against HM1.24

• Published in: Clinical cancer research 2005-05, Vol.11 (9), p.3377-3384
• Main Authors: REW, Steven B, PEGGS, Karl, SANJUAN, Irene, PIZZEY, Arnold R, KOISHIHARA, Yasuo, KAWAI, Shigeto, KOSAKA, Masaaki, OZAKI, Shuji, CHAIN, Benjamin, YONG, Kwee L
• Format: Article
• Language: English
• Subjects: Antigens, CD; Antineoplastic agents; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; cytotoxic T lymphocytes; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic - immunology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Flow Cytometry - methods; GPI-Linked Proteins; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Immunophenotyping; immunotherapy; Interferon-gamma - secretion; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocyte Common Antigens - immunology; Medical sciences; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - physiology; Multiple Myeloma - immunology; Multiple Myeloma - pathology; myeloma; Perforin; Pharmacology. Drug treatments; Plasma Cells - immunology; Pore Forming Cytotoxic Proteins; Signal Transduction - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes, Cytotoxic - immunology; Transfection
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-0650

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-γ ELISPOT assay (median, 342; range, 198-495 IFN-γ–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.