This technology is an IL10 fusion protein that can be used for the treatment of adenocarcinomas that are characterized by the overexpression of the oncogene Pim-1.
Cancers of the colon, breast, and prostate collectively account for 20% of cancer deaths in the U.S, therefore, there exists a significant need for new treatment methodologies. This technology provides a potential new treatment paradigm for adenocarcinomas that demonstrate high levels of the oncogene Pim-1. Overexpression of the oncogene Pim-1 has been linked to a subset of colon, breast, and prostate adenocarcinomas, and has been widely proposed as a therapeutic target. The inventors of this technology demonstrate that treatment with IL10 downregulates Pim-1 in an IL6-dependent manner in a mouse model of colon cancer and outline a method for using an IL10 fusion protein as a treatment for Pim-1 positive adenocarcinoma.
The short circulating plasma half-life of IL10 has previously precluded its use as a therapeutic. A well-established method of increasing circulatory time of proteins involves fusion to the Fc region of IgG. This invention utilizes a human IL10 IgG Fc fusion protein (IL10-Ig) to increase the circulation time of IL10 to more therapeutically-relevant timeframes. This IL10-Ig fusion protein has a half-life at least double that of normal IL10, and the inventors demonstrate an in vivo half-life of >3days in mice. Additionally, treatment of a mouse model of colon adenocarcinoma with a mouse IL10-Ig fusion protein results in normalized Pim-1 levels and an almost complete regression of tumor burden.
- Increased IL10 plasma circulation time
- Downregulation of the adenocarcinoma oncogene Pim-1 by an IL10-Ig fusion protein
- Administration of IL10-Ig fusion protein to mice demonstrated regression of colon adenocarcinoma in vivo