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

Authors' Affiliations: Departments of ¹ Haematology, and ² Immunology and Molecular Pathology, Royal Free and University College Medical School, London, United Kingdom; ³ Chugai Pharmaceutical Co. Ltd., Tokyo, Japan; ⁴ Tokushima Prefecture Hospital of Kaifu; and ⁵ University of Tokushima, Tokushima, Japan

Requests for reprints: Kwee L. Yong, Department of Haematology Royal Free and University College Medical School, 98 Chenies Mews, London WC1E 6HX, United Kingdom. Phone: 44-207-679-6139; Fax: 44-207-679-6222; E-mail: kwee.yong{at}ucl.ac.uk.

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- ELISPOT assay (median, 342; range, 198-495 IFN-–producing cells/10⁵ 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.

Key Words: immunotherapy • cytotoxic T lymphocytes • myeloma

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