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.
- 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
Zhang X, et al. Engineering of transgenic mice expressing human mesothelin for investigation of mesothelin-targeted therapeutics. [AACR Annual Meeting 2019 Abstract]
- Research Material: NIH will not pursue patent prosecution for this technology