Sperm protein 17 (Sp17) is a suitable target for immunotherapy of multiple myeloma.
Sperm protein 17 (Sp17) is a protein recently identified as a novel cancer-testis (CT) antigen in multiple myeloma (MM). Because this tumor antigen demonstrates a very restricted normal tissue expression, Sp17 may be an excellent target for tumor vaccine of MM. In this study, we determined the ability to generate Sp17-specific HLA class I-restricted cytotoxic T lymphocytes (CTLs) from the peripheral blood of 4 patients with MM, 3 consecutive Sp17(+) patients, and 1 Sp17(-) patient. Dendritic cells were generated from monocytes of 4 patients with MM and used to present a recombinant Sp17 protein to autologous T cells. Following 4 rounds of antigen stimulation, the CTLs were tested for their ability to kill autologous targets in an Sp17-dependent and HLA-class I- restricted manner in standard cytotoxicity assays. Despite previous chemotherapy and the immunosuppression so often associated with MM, CTL generation was successful in all 4 patients, irrespective of the Sp17 status of their tumors. Most importantly, the CTLs were able to lyse autologous tumor cells that expressed Sp17. Tumor cell lysis in all cases appeared to be mainly mediated by perforin and could be blocked by concanamycin A. We conclude that Sp17 is a suitable target for immunotherapy of MM. Our findings provide the basis for a clinical study aimed at inducing a cellular immune response directed at Sp17(+) MM.
Division of Hematology and Oncology, Texas Tech University Health Sciences Center, Amarillo 79106, USA.
Maurizio
M
Chiriva-Internati
Zhiqing
Z
Wang
Emanuela
E
Salati
Klaus
K
Bumm
Bart
B
Barlogie
Seah H
SH
Lim
D017951:Antigen Presentation; D000954:Antigens, Surface; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins; D009101:Multiple Myeloma / Q000473:pathology / Q000628:therapy*; D009363:Neoplasm Proteins / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000954:Antigens, Surface; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D052899:Pore Forming Cytotoxic Proteins; C090172:SPA17 protein, human; D054353:Perforin