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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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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.

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