Rew, SB and Peggs, K and Sanjuan, I and Pizzey, AR and Koishihara, Y and Kawai, S and Kosaka, M and Ozaki, S and Chain, B and Yong, KL (2005) Generation of potent antitumor CTL from patients with multiple myeloma directed against HM1.24. CLIN CANCER RES , 11 (9) 3377 - 3384.
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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/Tratio: 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.
|Title:||Generation of potent antitumor CTL from patients with multiple myeloma directed against HM1.24|
|Keywords:||CYTOTOXIC T-LYMPHOCYTES, STEM-CELL TRANSPLANTATION, PULSED DENDRITIC CELLS, ANTIGEN, IMMUNOTHERAPY, INDUCTION, MALIGNANCIES, VACCINATION, EXPRESSION, MECHANISM|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Infection and Immunity (Division of) > Research Department of Immunology|
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Wolfson Institute and Cancer Institute Administration > Cancer Institute > Research Department of Haematology
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