Humanized Mouse Model to Study Mesothelin (MSLN) -targeted Cancer Therapeutics: Bl6/TPO Mice


Mesothelin (MSLN) is an antigen highly expressed in several human cancers including mesotheliomas, ovarian cancers and pancreatic cancers. As such, human MSLN (hMSLN) is a target for many anti-cancer drugs. Most therapeutics targeting hMSLN do not recognize the mouse isoform of MSLN (mMSLN) and therefore cannot be tested in mouse cancer models. 

Investigators at the National Cancer Institute (NCI) have developed a mouse model wherein mice are genetically engineered to express hMSLN in the thyroid gland under the transcriptional control of a thyroid-specific (Tpo) gene promoter. Due to the tolerance to the hMSLN isoform, these mice are efficient recipients of cancer cell lines engineered to express hMSLN. These mice allow the testing of cancer therapeutics targeted against hMSLN in a fully immunocompetent animal background. In addition, these mice can be used to investigate on-target, off-tumor toxicity caused by hMSLN-directed therapeutics.

The NCI Laboratory of Molecular Biology is seeking parties interested in licensing this technology for commercialization in the field of cancer therapeutics and research targeting mesothelin-expressing tumors.



Potential Commercial Applications: Competitive Advantages:
  • Research, diagnostics, or therapeutics involving the target, mesothelin, such as in human mesotheliomas, ovarian cancers, pancreatic cancers
 
  • The humanized mice have expression of human mesothelin (hMSLN) that is localized to the thyroid. The Bl6/TPO mice are efficient recipients of cancer cells lines that express hMSLN
  • Endogenous expression of hMSLN in mice allows for the unique ability to test therapies that target human mesothelin, including studies off-target toxicity


Development Stage:
Prototype

Inventors:

Christine Alewine (NCI)  ➽ more inventions...

Serguei Kozlov

Xianyu Zhang (NCI)  ➽ more inventions...

Theresa Guerin


Intellectual Property:

Publications:
Zhang X, et al. Engineering of transgenic mice expressing human mesothelin for investigation of mesothelin-targeted therapeutics.  AACR Annual Meeting 2019 Abstract

Collaboration Opportunity:

Licensing only


Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515

OTT Reference No: E-096-2020
Updated: Aug 17, 2020