Abstract A25: Establishment and characterization of primary human Biomerk Tumorgraft™ Models: Application to oncology drug development

Abstract

Abstract One of the key challenges facing oncology drug development is the high attrition rates of compounds that enter the drug development pipeline, where very few achieve successful approval and marketing. Champions Biotechnology, in an effort to enhance the value of preclinical compounds and accelerate oncology drug development, has developed a novel preclinical platform derived from Biomerk Tumorgraft™ models; an innovative approach that utilizes the implantation of primary human tumors in immune-deficient mice in a manner that preserves the biological properties of the original human tumor. Biomerk Tumorgrafts™ differ from traditional xenograft models in that they are not passaged in tissue culture, and are instead exclusively passaged in vivo. Additionally, the Biomerk Tumorgraft™ models: (a) maintain the fundamental genotypic features of the original cancer, (b) represent the genetic heterogeneity of the cancer, and (c) do not change over several passages. Champions has established a bank of over 200 Tumorgraft models encompassing all major solid tumor types, all of which have been extensively characterized. Here we describe a panel of NSCLC lung, colon, and pancreatic tumorgraft models including gene expression profiling, mutational analyses and responses to standard of care agents. Of the NSCLC lung models, 6/8 demonstrated resistance to Erlotinib with 2/8 demonstrating an intermediate response, 2/6 also possessed a mutant K-ras or a mutant EGFR. Similarly, 3/6 K-ras mutant colon Tumorgraft models demonstrated sensitivity to irinotecan. In the case of the pancreatic models, 7/8 showed resistance to Erlotinib with the remaining model showing only a modest response. Through Champions' Personalized Oncology Services, we have also shown a high correlation between the Tumorgraft response and the clinical response. Together, these results demonstrate that each model differs with respect to its genetic composition and response to standard agents, and thus represents the efficacy of a compound on an individual patient. Given the diversity of models, the maintenance of the genomic and phenotypic characteristics of the original patient tumor, and the correlation between Tumorgraft and clinical responses, Champions Biomerk Tumorgraft™ models represent a novel preclinical in vivo platform capable of optimizing drug regimens for cancer patients and predicting the clinical effectiveness of preclinical drug candidates. Overall, the application of Biomerk Tumorgraft™ models has the potential to accelerate and enhance oncology drug development. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A25.