Humanized antibody(AvantGen, Inc.)

We report the development and characterization of a first-in-class humanized antibody to follicle-stimulating hormone (FSH). We have shown previously that blocking FSH action on its receptor increases bone mass, reduces body fat, and enhances energy expenditure. Furthermore, FSH has been reported to increase serum cholesterol. Therefore, an anti-FSH agent has the potential of preventing and treating obesity, osteoporosis, and hypercholesterolemia, diseases that affect millions of women and men worldwide. Our study provides the framework for further preclinical and subsequent clinical testing of our humanized antibody to FSH.

Breast cancer is the most prevalent cancer in women worldwide. About 15-20% of all breast cancers are triple negative breast cancer (TNBC) and are often highly aggressive when compared to other subtypes of breast cancers. To better characterize the biology that underlies the TNBC phenotype, we profiled the phosphotyrosine proteome of a panel of twenty-six TNBC cell lines using quantitative high resolution Fourier transform mass spectrometry. A heterogeneous pattern of tyrosine kinase activation was observed based on 1,789 tyrosine-phosphorylated peptides identified from 969 proteins. One of the tyrosine kinases, AXL, was found to be activated in a majority of aggressive TNBC cell lines and was accompanied by a higher level of AXL expression. High levels of AXL expression are correlated with a significant decrease in patient survival. Treatment of cells bearing activated AXL with a humanized AXL antibody inhibited cell proliferation and migration in vitro, and tumor growth in mice. Overall, our global phosphoproteomic analysis provided new insights into the heterogeneity in the activation status of tyrosine kinase pathways in TNBCs. Our approach presents an effective means of identifying important novel biomarkers and targets for therapy such as AXL in TNBC.