Drug Discovery Community Advances: Cell Proliferation Assay in a Mouse

Drug Discovery Community Advances: Cell Proliferation Assay in a Mouse

Healthcare Tech Outlook | Tuesday, April 16, 2019

Cellular proliferation was recently performed inside a mouse’s body. A hollow fiber filled with tumor cell suspension is implanted into the mouse. Hollow fibers are one millimeter in diameter and two centimeters in length and are implanted under the skin and into the peritoneum of the mouse. The fibers containing cells from up to three different tumor cell lines can get implanted into each location—six fibers per mouse. 

This fiber is allowed to remain inside the mouse, closing the ends of the fiber for a couple of weeks while the mouse receives treatment. The fiber doesn’t allow the tumor cells to move throughout the body, whereas nutrients, gases, and compounds can freely travel. Then, the fibers will be removed, and the antitumor effects of the compound would be evaluated by quantification of live cells. The membrane cut off is 500kDa which allows the antiproliferative effect of small molecule compound, antibodies, and antibody-drug-complexes. Thus, the hollow fiber model is a tool to select compound candidates as well as cell lines for successful in vivo xenograft testing.

The hollow fiber model was used in the drug discovery community in the field of anticancer drug development organization known as ProQinase. For a successful xenograft study, the hollow fiber model helps in compound prioritization. Then, a suitable tumor model is selected by analyzing the efficacy of the compounds against 12 cell lines in a single mouse study. Proof of target engagement and pharmacodynamic effects such as inhibition of enzyme activity, microtubule disruption, DNA damage, and cell cycle can be analyzed.

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A comprehensive study was performed to predict in vivo efficacy of more than 90 percent compounds. The hollow fiber model predicted the response of nine cell lines tests in the xenograft study. The results were 20 cell lines showing a predictive value of 92 percent.

The mice have an advantage as they are more economical for preselection of tumor model and compound candidates as they decrease the number of xenograft studies. The results are delivered in just two weeks.

The hollow fiber model changes the ways of drug discovery. The analysis is available at every lab in academics, pharma, and biotech for testing anticancer drugs which substantially speed up the process and increase the success rate of drug discovery.

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