myeloma Sperm protein 17 (Sp17)is a suitable target for immunotherapy of multiple

ABSTRACT Sperm protein 17 (Sp17) is a protein recently identified as a novel cancer-testis (CT) antigen in multiple myeloma (MM). Since this tumor antigen demonstrates a very restricted normal tissue expression, Sp17 may be an excellent target for tumor vaccine of MM. In this present study, we determined the ability to generate Sp17-specific HLA-class I restricted CTLs from the peripheral blood of 4 patients with MM, 3 consecutive Sp17-positive patients and one Sp17-negative patient. Dendritic cells were generated from monocytes of four patients with MM and used to present a recombinant Sp17 protein to autologous T cells. Following four 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 multiple myeloma, CTL generation was successful in all 4 patients, irrespectively 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 perforin-mediated and could be blocked by Concanamycin A. We conclude that Sp17 is a suitable target for immunotherapy of multiple myeloma. Our findings provide the basis for a clinical study aimed at inducing a cellular immune response directed at Sp17-positive MM.From bloodjournal.hematologylibrary.org by guest on May 29, 2013. For personal use only.