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Immunocompetent Mouse Model for Tracking Cancer Progression

Posted Jun 30 2011 8:00pm

Description of Invention:
The technology is a transgenic mouse model tolerized to firefly Luciferase (ffLuc)- and enhanced green fluorescent protein (eGFP)-labeled tissue whilst maintaining normal immune function. Luc and eGFP are the most frequently used bioimaging markers to track cancer progression in pre-clinical mouse models. As these markers are immunogenic, their reporter activity becomes diminished over time and so their use has largely been limited to immunodeficient mice. However, immune function is crucial for tumor development and progression, making the use of immunocompetent mice more desirable.

The immunocompetent mouse model described in this invention was generated using the rat growth hormone gene promoter (rGH) to target ffLuc-eGFP fusion gene expression to the pituitary gland, restricting any resulting interfering reporter signal within the head. This allows the tracking of cancer progression throughout the body, where the reporter activity of introduced ffLuc/eGFP-labeled tumors is maintained, despite normal immune function. These immunocompetent rGH-ffLuc-eGFP transgenic mice can be used as hosts in cancer models, allowing long-term in vivo monitoring of the progression of ffLuc/eGFP-labeled tumor cells in the body, which may lead to more clinically relevant insights into cancer progression, metastases and response to therapies.

Applications:
  • In vivo model for studying tumor progression and testing anti-cancer therapeutics using ffLuc or eGFP labeling for bioimaging.
  • Since rGH-ffLuc-eGFP is also a growth hormone-responsive reporter, these rGH-Luc-GFP mice may also be used to screen growth-hormone stimulating drugs for treating Achondroplasia (dwarf syndrome) or as a test for illegal performance-enhancing drugs.


Advantages:
  • This technology represents a more clinically relevant in vivo model of cancer progression for testing anti-cancer therapeutics.
  • This immunocompetent mouse model is more desirable as a pre-clinical model over the currently used immunodeficient mouse models as immune function is crucial for tumor development and progression.


Development Status:
  • Early-stage
  • Pre-clinical
  • In vitro data available
  • In vivo data available (animal)


Inventors:
Glenn Y Merlino (NCI)
Chi-Ping Day (NCI)


Patent Status:
HHS, Reference No. E-173-2010/0

Research Tool — Patent protection is not being pursued for this technology.

Relevant Publication:
  1. Day CP, et al. Preclinical therapeutic response of residual metastatic disease is distinct from its primary tumor of origin. Int J Cancer. 2011 Feb 10, doi: 10.1002/ijc.25978. [Epub ahead of print] [ PMID: 21312195 ]
  2. Day CP, et al. Lentivirus-mediated bifunctional cell labeling for in vivo melanoma study. Pigment Cell Melanoma Res. 2009 Jun;22(3):283-295. [ PMID: 19175523 ]
  3. Luque RM, et al. Reporter expression, induced by a growth hormone promoter-driven Cre recombinase (rGHp-Cre) transgene, questions the developmental relationship between somatotropes and lactotropes in the adult mouse pituitary gland. Endocrinology. 2007 May;148(5):1946-1953. [ PMID: 17289844 ]
  4. Latta-Mahieu M, et al. Gene transfer of a chimeric trans-activator is immunogenic and results in short-lived transgene expression. Hum Gene Ther. 2002 Sep 1;13(13):1611-1620. [ PMID: 12228016 ]
  5. Stripecke R, et al. Immune response to green fluorescent protein: implications for gene therapy. Gene Ther. 1999 Jul;6(7):1305-1312. [ PMID: 10455440 ]
  6. Liao CP, et al. Mouse models of prostate adenocarcinoma with the capacity to monitor spontaneous carcinogenesis by bioluminescence or fluorescence. Cancer Res. 2007 Aug 1;67(15):7525-7533. [ PMID: 17671224 ]


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The National Cancer Institute Center for Cancer Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immunocompetent rGH-ffLuc-eGFP transgenic mice. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


For Licensing Information Please Contact:
Sabarni Chatterjee Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: chatterjeesa@mail.nih.gov
Phone: 301-435-5587
Fax: 301-402-0220


Ref No: 2280

Updated: 07/2011

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