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A Preclinical Model for Mutant Human EGFR-driven Lung Adenocarcinoma

Summary
The National Cancer Institute (NCI) has a human epidermal growth factor receptor- (EGFR) driven tumor mouse model of lung adenocarcinoma available for licensing.
NIH Reference Number
E-041-2014
Product Type
Keywords
  • Lung cancer, Lung Adenocarcinoma, Epidermal Growth Factor Receptor, EGFR, Respiratory, Mouse Model, Genetically Engineered Mouse, GEM, Ohler Weaver
Collaboration Opportunity
This invention is available for licensing.
Contact
Description of Technology

Previously described epidermal growth factor receptor- (EGFR) driven tumor mouse models develop diffuse tumors, which are dissimilar to human lung tumor morphology and difficult to measure by CT and MRI scans. Scientists at the National Cancer Institute (NCI) have developed and characterized a genetically engineered mouse (GEM) model of human EGFR-driven tumor model (hEGFR-TL) that recapitulates the discrete lung tumor nodules similar to those found in human lung tumor morphology. Individual tumor nodules can be easily measured by live animal imaging and the nodules can be harvested and isolated from surrounding lung tissue post-treatment, making this a more tractable model for human non-small cell lung adenocarcinoma. The lungs express an EGFR transgene that harbors two mutations (‘L858R’ and ‘T790M’) which render the lung tumors resistant to first generation EGFR inhibitors and are useful for evaluating drugs targeting resistant tumors.

MRI scan showing lung tumor nodule in EGFR-TL mouse and a Lung tumor nodule in EGFR-TL mouse stained with antibody to EGFR

Potential Commercial Applications
  • Preclinical in vivo screen of therapeutics targeting tumor kinase inhibitors such as EGFR-mediated lung tumors, and identification of new biomarkers in this pathway 
  • Evaluation of novel therapeutics in inducible models of EGFR-driven drug resistant lung adenocarcinoma
  • Dermatology Research
  • Immunology, Inflammation and Autoimmunity Research
Competitive Advantages
  • Lung tumor development and response to drugs can be monitored by MRI or CT scanning
  • Contain a human EGFR transgene (either TRE-EGFR-L858R or TRE-EGFR-L858R-T790M models are available) and an activating transgene (CCSP-rtTA) to direct expression of mutant EGFR to the Clara cells
Inventor(s)

Simone Difilippantonio Ph.D., Zoe Weaver Ohler Ph.D. (NCI), Deborah Householder (NCI/CAPR)

Development Stage
Publications

Nakamura Y, et al., Near infrared photoimmunotherapy in a transgenic mouse model of spontaneous epidermal growth factor receptor (EGFR)-expressing lung cancer.  [PMC 5335921]

Patent Status
  • Research Material: NIH will not pursue patent prosecution for this technology
Therapeutic Area
Posted
Wednesday, January 15, 2020