Cancer immunotherapy targeting Sp17: when should the laboratory findings be translated to the clinics?

Despite advances in chemotherapeutic agents, the prognosis for some cancers remains extremely poor, suggesting the need for other treatment modalities. Immunotherapy appears an ideal approach because the mechanisms of tumor cell killing induced by tumor vaccines are different from those from chemotherapy. Various investigations are ongoing to identify suitable targets for this purpose. Sperm protein 17 (Sp17) was originally identified by our group as a novel cancer-testis antigen in various malignancies, including multiple myeloma. Sp17 is a highly immunogenic protein and the observation that more than 90% of vasectomized males develop immunity against Sp17 suggests the opportunity and safety of Sp17 for tumor vaccines. Recent works by other workers suggest a low level of expression of Sp17 in some normal tissues, and investigators have questioned whether Sp17 is in fact a suitable target for immunotherapy. In this paper, we review the general principles of immunotherapy and provide evidence supporting the highly immunogenic nature of Sp17. We also address the discrepancies between the objectives of oncologists involved in treating cancer patients and their familiarity with acceptable levels of toxicity of any effective therapy and those of pure laboratory-based investigators. Finally, we present some early clinical data supporting the rationale for further investigations of Sp17 for tumor vaccines. Copyright 2005 Wiley-Liss, Inc.