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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3538-3545.
Prepublished online as a Blood First Edition Paper on July 21, 2005; DOI 10.1182/blood-2005-04-1438.


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NEOPLASIA

Induction of HM1.24 peptide–specific cytotoxic T lymphocytes by using peripheral-blood stem-cell harvests in patients with multiple myeloma

Ali Jalili, Shuji Ozaki, Tomoko Hara, Hironobu Shibata, Toshihiro Hashimoto, Masahiro Abe, Yasuhiko Nishioka, and Toshio Matsumoto

From the Department of Medicine and Bioregulatory Sciences, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan; Division of Transfusion Medicine, Tokushima University Hospital, Tokushima, Japan; and Department of Internal Medicine and Molecular Therapeutics, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.

HM1.24 antigen is preferentially overexpressed in multiple myeloma (MM) cells but not in normal cells. To explore the potential of HM1.24 as a target for cellular immunotherapy, we selected 4 HM1.24-derived peptides that possess binding motifs for HLA-A2 or HLA-A24 by using 2 computer-based algorithms. The ability of these peptides to generate cytotoxic T lymphocytes (CTLs) was examined in 20 healthy donors and 6 patients with MM by a reverse immunologic approach. Dendritic cells (DCs) were induced from peripheral-blood mononuclear cells of healthy donors or peripheral-blood stem-cell (PBSC) harvests from patients with MM, and autologous CD8+ T cells were stimulated with HM1.24 peptide–pulsed DCs. Both interferon-{gamma}–producing and cytotoxic responses were observed after stimulation with either HM1.24-126 or HM1.24-165 peptides in HLA-A2 or HLA-A24 individuals. The peptide-specific recognition of these CTLs was further confirmed by tetramer assay and cold target inhibition assay. Importantly, HM1.24-specific CTLs were also induced from PBSC harvests from patients with MM and these CTLs were able to kill MM cells in an HLA-restricted manner. These results indicate the existence of functional DCs and HM1.24-specific CTL precursors within PBSC harvests and provide the basis for cellular immunotherapy in combination with autologous PBSC transplantation in MM.


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