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Clin Cancer Res. 2005 May 1;11(9):3377-84.

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

Author information

1
Department of Haematology, Royal Free and University College Medical School, London, United Kingdom.

Abstract

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.

PMID:
15867238
DOI:
10.1158/1078-0432.CCR-04-0650
[Indexed for MEDLINE]
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