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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-02-0408.

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2002-02-0408v1
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Blood, 1 August 2002, Vol. 100, No. 3, pp. 961-965

NEOPLASIA

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

Maurizio Chiriva-Internati, Zhiqing Wang, Emanuela Salati, Klaus Bumm, Bart Barlogie, and Seah H. Lim

From the Division of Hematology and Oncology, Texas Tech University Health Sciences Center, Amarillo; Blood Stem Cell Transplantation Program, Don and Sybil Harrington Cancer Center, Amarillo, TX, and Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock, AR.

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.

© 2002 by The American Society of Hematology.
 

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