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4 March 2019 Predicting antibody penetration in a first-in-human clinical trial of head and neck cancers (Conference Presentation)
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Abstract
Low response rates in solid tumors including head and neck cancers (HNCs) have been attributed to failure of the drug to reach its intended target. However, investigation of drug delivery has been limited due to difficulties in measuring concentrations in the tumor and the ability to localizing drugs in human tissues. Factors determining intratumoral antibody distribution in primary tumor and metastatic lymph nodes have not been well-studied in human patients. To address this challenge, we propose to leverage fluorescently labeled antibodies to investigate antibody delivery into HNCs. To this end, we have conducted a first-in-human clinical trial to assess the delivery of panitumumab-IRDye800 in HNCs. Twenty-two patients enrolled in this study received intravenous administration of panitumumab-IRDye800 at multiple subtherapeutic doses: (1) 0.06mg/kg, (2) 0.5 mg/kg, (3) 1 mg/kg, (4) 50 mg flat dose, (5) 25 mg flat dose. To quantify the antibody delivery, fresh tumor samples were procured and the amount of antibody in the tumor was quantified as ng/mg of tissue, which was then correlated with tumor characteristics. Immunohistochemistry of multiple protein markers, including EGFR, ERG, cytokeratin, Ki67, alpha-smooth muscle actin, etc., have been implemented in serial sections of primary tumors and metastatic lymph nodes. A quantitative image analysis pipeline was developed to analyze these IHC images and score the staining on both global and local scale. A predictive model was built to identify the most important predictors for antibody penetration from pharmacological factors, tumor pathophysiological factors, and tumor microenvironmental factors.
Conference Presentation
© (2019) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
Guolan Lu, Shayan Fakurnejad, Brock Martin, Ashley Zhu, Nynke van den Berg, Stan van Keulen, Quan Zhou, Tarn Teraphongphom, Rebecca Gao, Nicholas Oberhelman, Stefania Chirita, Robert Erstey, Christina Kong, Dimitrios Colevas, and Eben Rosenthal "Predicting antibody penetration in a first-in-human clinical trial of head and neck cancers (Conference Presentation)", Proc. SPIE 10859, Visualizing and Quantifying Drug Distribution in Tissue III, 1085905 (4 March 2019); https://doi.org/10.1117/12.2513258
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