Induction of HM1.24 peptide-specific cytotoxic T lymphocytes by using peripheral-blood stem-cell harvests in patients with multiple myeloma.
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.
Jalili
Ali
A
Department of Medicine and Bioregulatory Sciences, Institute of Health Biosciences, University of Tokushima Graduate School, Japan.
Ozaki
Shuji
S
Hara
Tomoko
T
Shibata
Hironobu
H
Hashimoto
Toshihiro
T
Abe
Masahiro
M
Nishioka
Yasuhiko
Y
Matsumoto
Toshio
T
D015703:Antigens, CD; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D058851:GPI-Linked Proteins; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D059871:HLA-A24 Antigen; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000494:pharmacology; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous; D000074010:Bone Marrow Stromal Antigen 2
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D007371:Interferon-gamma; D008562:Membrane Glycoproteins; D010455:Peptides; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2