The invention listed below is owned by an agency of the U.S. Government and is available for licensing and/or co-development in the U.S. in accordance with 35 U.S.C. 209 and 37 CFR part 404 to achieve expeditious commercialization of results of federally-funded research and development.
Before testing drugs in humans, drug developers are required to demonstrate a reasonable expectation of safety and efficacy by performing so-called pre-clinical studies. A key element of such trials is the use of animal models, typically mice or rats that are selected for demonstrating hallmarks of a given disease. For cancer research, while many mouse models exist to simulate the response of the cancer to a particular drug, all of the current models have some limitations in their ability to fully predict the concomitant physiological or immunological response that might result when the drug progresses to clinical trials. This is problematic both in models in which the cancer spontaneously develops in the animal as well as models in which cancerous cells or tumors, i.e. allografts (derived from cells of the same organism) or xenografts (derived from cells of different organism, usually humans) are transplanted into an otherwise cancer-free animal.
To address these issues, researchers at NCI have developed a means of more closely simulating in mouse models both melanoma cancer itself and the resulting physiological an immunological response by creating a genetically engineered mice (GEM)-derived allograft (GDA). This allograft both resembles human-like melanoma and has features that will stimulate a normal immunological response in the mouse. Thus, when transplanted into a host, the resulting tumor-containing mouse may be used to test conventional cancer therapies (e.g., chemotherapy and radiotherapy), targeted drugs (e.g., kinase inhibitors), and immunotherapies with an expectation that the response in the mouse will more closely mimic the types of responses expected in humans if the therapy progresses to clinical trials. Further this melanoma-based GDA approach may represent a new standard for building or improving preclinical models of other types of cancer.
- Hgf-tg;Cdk4R24C C57BL/6 mouse-derived melanoma allograft with humanized pathogenetics allows adoption of clinically relevant procedures and endpoints, facilitating clinical translation.
- Features a constitutively activated MET/MAPK pathway and disrupted CDKN2A pathway.
- Expresses typical diagnostic markers of human melanoma such as DCT and TRP1.
- Exhibits progression patterns relevant to human disease.
- A mouse allograft model that provides a preclinical model of human-like advanced-stage melanoma.
- Allograft model may be useful for preclinical testing of conventional cancer therapies, targeted cancer therapies, and cancer immunotherapies.