Antigen-targeted Therapy for Head and Neck Cancer
Head and neck cancers have devastating effects on patient mortality and morbidity despite aggressive therapy. Head and neck squamous cell carcinoma (HNSCC) tumors are associated with various stromal cells, and these cells are active contributors to neoplastic transformation. The most abundant stromal cells in the HNSCC tumor microenvironment are tumor associated fibroblasts (TAFs). We previously reported that TAFs facilitate HNSCC growth and metastasis. In addition, we reported that TAFs, but not HNSCC cell lines, secrete hepatocyte growth factor (HGF); HGF was initially discovered as a mitogen that promoted growth of hepatocytes, epithelial tissues, endothelial cells, and melanocytes on binding to the c-Met receptor. In addition, fibroblast-secreted HGF was found to dissociate epithelial cells and to induce a more invasive phenotype in several carcinoma cell lines. Humanized antibodies targeting specific tumor-antigens have been shown to have antitumor efficacy in HNSCC. Ficlatuzumab is a humanized IgG1 HGF-inhibitory monoclonal antibody that binds HGF with a high affinity and specificity. Preclinical trials have shown that ficlatuzumab effectively binds HGF and has antitumor effects on NSCLC and glioma preclinical models. We demonstrate that neutralizing TAF-derived HGF with ficlatuzumab effectively mitigates c-Met signaling and decreases HNSCC proliferation, migration, and invasion. Thus, ficlatuzumab effectively mitigates stromal influences on HNSCC progression. Together, these findings strongly suggest that ficlatuzumab may be efficacious in treating HNSCC.
Speaker: Sufi Thomas, PhD
Sufi Thomas, PhD, is an Associate Professor of Otolaryngology at the University of Kansas Medical Center. In addition, she holds secondary appointments in the Departments of Cancer Biology, and Anatomy and Cell Biology. She completed her PhD at the University of Mumbai in India and post-doctoral training at the University of Pittsburgh under the direction of Dr. Jennifer Grandis. Dr. Thomas specializes in head and neck cancer translational research. She has published extensively and developed several therapeutic approaches that have been tested in clinical trials. She is currently delineating the mechanism where by the tumor microenvironment and in particular tumor-associated fibroblasts facilitate head and neck cancer progression and response to therapy.
Speaker: Karen McCord
Karen McCord is Chief Executive Officer of Breezio, an online community engagement software company. Breezio’s patented technology allows organizations to curate, contribute to and grow knowledge. During the past year as CEO she was a finalist for the Start-up Maryland’s Contest, has been a panelist at scholarly publishing conferences and taken the company from pre-revenue to a revenue generating entity. Ms. McCord’s experience includes managing international teams for both technical and financial projects in global public health where she helped raise over $300 million towards HIV prevention efforts and most recently she was involved with an evaluation project of a large research enterprise in the Middle East. In September 2014, Karen won the “Make it Matter Challenge”, an innovation contest sponsored by LinkedIn and the Taproot Foundation, aimed at securing ideas to connect nonprofits to quality pro bono resources. Ms. McCord completed the Management and Technology Dual Degree Program at the University of Pennsylvania, with bachelor degrees from the School of Engineering and Applied Science and the Wharton School.
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