Successful generation of sperm protein 17 (Sp17)-specific cytotoxic T lymphocytes from normal donors: implication for tumour-specific adoptive immunotherapy following allogeneic stem cell transplantation for Sp17-positive multiple myeloma.
Sperm protein 17 (Sp17) is a highly immunogenic cancer-testis antigen expressed by tumour cells from up to 30% of patients with multiple myeloma (MM). We recently successfully generated Sp17-specific human leucocyte antigen (HLA)-A1 and B27-restricted cytotoxic T lymphocytes (CTLs) from the peripheral blood of a healthy donor. Because CTLs were able to kill HLA-matched fresh myeloma cells, it may be possible to generate and administer myeloma-specific donor T cells to MM patients following allogeneic stem cell transplantation to enhance graft-versus-myeloma (GVM) without inducing graft-versus-host disease (GVHD). To determine how widely applicable this approach is, we have determined the ability to generate Sp17-specific CTLs from four consecutive healthy donors with other HLA class I phenotypes. We found that Sp17-specific HLA class I-restricted CTLs could be easily generated from all four donors. Sp17-specific CTLs were primarily CD8 in phenotype and produced interferon-gamma and very little interleukin-4. These T cells killed target cells primarily via the perforin-mediated route. These results therefore suggest that myeloma-specific donor T-cell infusion that targets Sp17 to selectively enhance GVM could be applicable to patients with Sp17+ MM.
Chiriva-Internati
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Division of Hematology and Oncology, Texas Tech University School of Medicine at Amarillo and Blood Stem Cell Transplant Program, Don and Sybil Harrington Cancer Center, Amarillo, TX 79106, USA.
Wang
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Z
Salati
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Wroblewski
D
D
Lim
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SH
D000328:Adult; D000951:Antigens, Neoplasm / Q000276:immunology*; D000954:Antigens, Surface; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D020350:Graft vs Tumor Effect / Q000276:immunology*; D015788:HLA-A1 Antigen / Q000276:immunology; D015796:HLA-B27 Antigen / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D017710:Lymphocyte Transfusion; D008297:Male; D008565:Membrane Proteins; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D009363:Neoplasm Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D033581:Stem Cell Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology*
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D015788:HLA-A1 Antigen; D015796:HLA-B27 Antigen; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C090172:SPA17 protein, human