Generation of potent antitumor CTL from patients with multiple myeloma directed against HM1.24.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
Our results indicate that HM1.24 is a promising target for immunotherapy of multiple myeloma.
Rew
Steven B
SB
Department of Haematology, Royal Free and University College Medical School, London, United Kingdom.
Peggs
Karl
K
Sanjuan
Irene
I
Pizzey
Arnold R
AR
Koishihara
Yasuo
Y
Kawai
Shigeto
S
Kosaka
Masaaki
M
Ozaki
Shuji
S
Chain
Benjamin
B
Yong
Kwee L
KL
D015703:Antigens, CD; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D058851:GPI-Linked Proteins; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology; D054353:Perforin; D010950:Plasma Cells / Q000276:immunology; D052899:Pore Forming Cytotoxic Proteins; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D000074010:Bone Marrow Stromal Antigen 2
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D008562:Membrane Glycoproteins; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2