AACR 2014: The Champions TumorGraft® Bank: A Demographically-Rich Repository of Preclinical TumorGraft Models
The Champions TumorGraft® Bank: A demographically-rich repository of preclinical TumorGraft models
Tin Khor1, David Vasquez1, Amanda Katz1, Gilson Baia1, Daniel Ciznadija1, David Sidransky2, Keren Paz1.1Champions Oncology, Inc., Baltimore, MD; 2Johns Hopkins University, Baltimore, MD
Many oncology pharmaceuticals fail during phased clinical trials, having been advanced based on research using flawed preclinical models that do not accurately replicate human tumor biology. For example, numerous models are based on genetically-engineered mice, which are often generated from limited numbers of genetic aberrations. As such, they may not accurately represent either the chaotic heterogeneity that exists within intact human tumors or throughout the clinical population. TumorGrafts, in which patient-derived tumor tissue is directly engrafted into immunodeficient mice, offer a step forward in this unresolved issue. These models maintain the complex intra-tumoral heterogeneity and biology of an intact malignancy, as well its 3-dimensional interplay with stromal components and other cells fluxing into the immediate environment. The intrinsic cross-talk between the different compartments of the tumor is also retained.
We wanted to generate a repository of these tumor models and make them available to the research community for use in pharmaceutical development and basic research processes. Here we describe our extensive bank of live TumorGrafts comprising a range of different tumor types, from more common cancers, including lung, colon, and breast, to a number of rare subtypes such as adenoid cystic carcinoma. These models were originally developed for personalizing cancer treatments and are derived from patient populations across all ages and ethnicities, encompassing both treatment-naïve and heavily-treated individuals. Furthermore, because of our distinct patient-focus, we maintain detailed clinical histories, as well as molecular data where available. Hence, the bank is a reasonable surrogate of the population from which treatment groups are typically drawn for clinical trials and could potentially be of value for predetermining target populations for therapeutic intervention. The Champions TumorGraft® Bank provides superior pre-clinical models that faithfully capture all the biological and molecular features of cancer and can serve basic and clinical research groups as an increasingly valuable source for drug development and biomarker discovery.