BackgroundTriple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no effective standard therapy. Breast cancer stem-like cells (BCSCs) in primary TNBCs are reported to be responsible for metastatic spread of the disease and resistance to chemotherapy, but no available therapeutic tools target BCSCs. We previously reported that the ganglioside GD2 is highly expressed on BCSCs and that inhibition of its expression hampers TNBC growth. We therefore hypothesized that the anti-GD2 antibody dinutuximab (ch14.18) targets GD2+ BCSCs and inhibits TNBC growth.MethodTo test our hypothesis, we first determined GD2 expression via immunohistochemistry in frozen primary tumor samples from patients with TNBC (n=89). Then, we examined the effects of dinutuximab on TNBC cell adhesion, migration, and mammosphere formation in vitro and on tumor growth in vivo using TNBC cell-line and patient-derived xenograft (PDX) models.ResultsWe found that GD2 was expressed in around 60% of primary TNBC tumors at variable levels and was associated with worse overall survival of patients with TNBC (p=0.002). GD2 was found to be expressed in tumors and stroma, but normal ducts and lobules in adjacent tissues have shown low or no GD2 staining, indicating that GD2 is potentially a novel biomarker for tumor and its microenvironment. Treatment with dinutuximab significantly decreased adhesion and migration of MDA-MB-231 and SUM159 TNBC cells. Moreover, dinutuximab treatment inhibited mTOR signaling, which has been shown to be regulated by GD2 in BCSCs. Dinutuximab also reduced tumor growth in nude mice bearing TNBC cell-line xenografts. Finally, dinutuximab in combination with activated natural killer cells inhibited tumor growth in a TNBC PDX model and improved overall survival of tumor-bearing mice.ConclusionsDinutuximab successfully eliminated GD2+ cells and reduced tumor growth in both in vivo models. Our data provide proof-of-concept for the criticality of GD2 in BCSCs and demonstrate the potential of dinutuximab as a novel therapeutic approach for TNBC.

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We observed that the immune checkpoint protein B7-H3 is overexpressed in acute myeloid leukemia (AML) patients with poor treatment outcomes. Inhibition of B7-H3 expression or blocking of its activity using a novel monoclonal antibody (T-1A5) in AML cells significantly enhanced NK cell-mediated cytotoxicity in AML cells in vitro and in vivo. Moreover, human-mouse chimera of this antibody (ChT-1A5) induced antibody-dependent cell-mediated cytotoxicity (ADCC) in B7-H3+ primary AML cells, but not in normal hematopoietic cells, suggesting the specify of this antibody for AML cells. Epitope mapping studies identified that both T-1A5 and ChT-1A5 antibodies bind to the FG-loop region of B7-H3, which is known to regulate the immunosuppressive function of B7-H3. Furthermore, treatment with ChT-1A5 in combination with human NK cells significantly prolonged survival in AML patient-derived xenograft models. Our results suggest that ChT-1A5 antibody can inhibit the immunosuppressive function of B7-H3 protein as well as induce ADCC in B7-H3+ AML.

Background: In the absence of strict regulations, the extent of exposure to Bisphenol A (BPA) toxicity depends mainly on the consumers' own knowledge, attitude, and practices about the matter. The aim of this study was to assess the current level of familiarity and knowledge about BPA, attitude towards it, practices related to the use of BPA-containing products, and the predictors of each. Methods : We carried out a cross-sectional study among students at the American University of Beirut, Lebanon, between January and April 2017. Full-time students above the age of 18 and registered in a specific major were eligible to participate in the study. An English questionnaire that assesses familiarity, as well as knowledge, attitude, and practice (KAP) was developed based on current literature and expert opinion. Demographics, lifestyle, and level of familiarity with the topic were assessed among all participants. Predictors of familiarity, defined as knowing at least a little about BPA, were assessed among all participants using bivariate and multivariate analyses. Among students familiar with BPA, predictors of higher KAP scores were assessed by similar analyses. Adjusted odds ratios (OR) with 95% confidence interval (CI) were reported. Results : The level of familiarity with BPA was 23.7%.Studying in a health-related field was a predictor of familiarity (adjusted OR=3.11; CI: 2.08-4.66).

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