Anti-Sp17 monoclonal antibody-doxorubicin conjugates as molecularly targeted chemotherapy for ovarian carcinoma.

Sperm protein 17 (Sp17) is selectively overexpressed in several human malignancies including ovarian carcinoma, but is absent or expressed at low levels in most normal tissues. Previous work from our group characterized an anti-Sp17 monoclonal antibody (clone 3C12) and showed that it specifically targeted tumor cells. In this report, we investigated whether a novel immunoconjugate containing 3C12 linked to the chemotherapeutic agent doxorubicin [(DOX) Adriamycin] had antitumor activity against ovarian cancer cell lines and tumor models. DOX was conjugated to 3C12 using a linker, and the specificity of 3C12-DOX was examined in Sp17-positive SKOV3 and Sp17-negative COC2 ovarian cancer cells using cell-based ELISA and internalization assays. The cytotoxicity of 3C12-DOX was assessed with the MTT assay, and its therapeutic effectiveness was evaluated in immunodeficient mice bearing SKOV3 cells. In vitro, the 3C12-DOX immunoconjugate specifically bound to and was internalized by Sp17-positive SKOV3 cells but did not bind to Sp17-negative cells. Treatment with 3C12-DOX (0.001 to 10 µg/mL) decreased the viability of SKOV3 cells in a Sp17-specific manner. In vivo, 3C12-DOX (3 mg/kg) induced the regression of established SKOV3 xenograft tumors in BALB/c mice compared with control treatment. The antitumor effects of 3C12-DOX were significantly associated with the induction of apoptosis in tumor cells. In addition, 3C12-DOX showed no observable adverse effects or toxicity when compared with DOX alone in mice bearing ovarian tumor xenografts. Our findings suggest that 3C12-DOX may be a potential antibody-drug conjugate for clinical development.

Sperm protein 17, MAGE-C1 and NY-ESO-1 in hepatocellular carcinoma: expression frequency and their correlation with clinical parameters.

UNLABELLED: This study is dedicated to investigate the expression patterns of sperm protein 17 (Sp17), melanoma-specific antigen (MAGE)-C1 and New York esophageal squamous cell carcinoma-1 (NY-ESO-1), to explore the correlation between these cancer-testis antigens and clinical parameters, and to evaluate their values in diagnosis and differentiation of hepatocellular carcinoma. METHODS: Immunohistochemical staining was performed in 45 paraffin-embedded hepatocellular carcinoma specimens. 45 normal peripheral hepatic tissues collected from adjacent non-cancerous areas were used as controls. RESULTS: Positive results of immunohistostaining were obtained in 16 (35.6%), 7 (15.6%) and 36 (80.0%) samples using MAGE-C1, NY-ESO-1 and Sp17 antibodies, respectively. The immunoreactivity of Sp17 was also found in 7 (14.0%) control samples. A statistical correlation between the frequency of Sp17 expression and tumor differentiation grade in hepatocellular carcinoma was confirmed. CONCLUSIONS: Sp17 is highly expressed in hepatocellular carcinoma cells. The frequency of Sp17 expression is closely related to the pathologic differentiation in hepatocellular carcinoma.

Surveillance study of species distribution, antifungal susceptibility and mortality of nosocomial candidemia in a tertiary care hospital in China.

BACKGROUND: Bloodstream infections due to Candida species cause significant morbidity and mortality, and the epidemiology of Candida infection is changing. Surveillance for candidemia is necessary to detect trends in species distribution and antifungal resistance. METHODS: The medical and electronic records of all patients who had candidemia at the authors' hospital from 2009 to 2011 were reviewed for demographic data and clinical information, including the infecting Candida species, resistance to antifungals and survival, and the presence of risk factors associated with candidemia. RESULTS: A total of 133 distinct episodes of candidemia were identified over the study period. The annual incidence of candidemia ranged between 0.71 and 0.85 cases/1000 hospital discharges. The most frequent Candida species were C. tropicalis (28.6%), followed by C. albicans (23.3%) and C. parapsilosis (19.5%). The rates of susceptibility to antifungal agents were as followed: voriconazole (97.8%), itraconazole (69.5%), fluconazole (46.1%), ketoconazole (38.9%). Out of 131 evaluable patients, 34 (26.0%) died within 30 days from the onset of candidemia. C. tropicalis candidemia was associated with the highest mortality rate (44.7%). Regarding the crude mortality in the different units, patients in Hemato-Oncology ward had the highest mortality rate (66.7%), followed by patients in cardiovascular wards and ICU (57.1% and 25.6%, respectively). Predictors of 30-day mortality were identified by uni- and multivariate analyses. Complicated abdominal surgery, presence of central venous catheter (CVC), neutropenia, candidemia due to C. tropicalis and poor treatment with fluconazole were significantly associated with the 30-day mortality. Presence of CVC (odds ratio[OR] = 4.177; 95% confidence interval [CI] = 1.698 to 10.278; P = 0.002) was the only independent predictor for mortality in the multivariate analysis. CONCLUSION: This report provides baseline data for future epidemiological and susceptibility studies and for the mortality rates associated with candidemia in our hospital. The knowledge of the local epidemiological trends in Candida species isolated in blood cultures is important to guide therapeutic choices.

Anti-Sp17 monoclonal antibody with antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity activities against human ovarian cancer cells.

Sperm protein 17 (Sp17) is a cancer testis antigen that has been shown to be overexpressed in a variety of gynecologic malignancies, in particular ovarian cancer. Emerging evidences indicate that Sp17 is involved in tumorigenesis and in the migration of malignant cells. It has been proposed as a useful target for tumor-vaccine strategies and a novel marker to define tumor subsets and predict drug response. However, the antitumor activity of anti-Sp17 monoclonal antibody (anti-Sp17 mAb) has not been investigated. In this study, the in vitro cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities of anti-Sp17 mAb were evaluated using Sp17-positive ovarian cancer cells as targets, Sp17-negative ovarian cancer cells as the control, and healthy human peripheral blood monocytes and healthy human serum as effectors. Our preliminary results indicate that the direct cytotoxicity of anti-Sp17 mAb against the investigated ovarian cancer cells was very weak. However, the cytotoxicity of anti-Sp17 mAb, mediated by peripheral blood mononuclear cells (PBMCs), as ADCC, or by human serum, as CDC, was relatively strong in the Sp17-positive ovarian cancer cells. This finding suggested that anti-Sp17 mAb could be a useful tool against ovarian cancer and may provide insight into the development of low side-effect targeting therapy for this malignant disease.