Abstract
The Knight Cancer Institute at Oregon Health Sciences University in Portland and Organovo of San Diego, CA, are collaborating to develop 3-dimensional tumor models for preclinical drug testing.
Researchers at the Knight Cancer Institute at Oregon Health Sciences University (OHSU) in Portland will collaborate with tissue engineering company Organovo of San Diego, CA, to develop 3-dimensional (3D) tumor models for preclinical drug testing. The company says these models, made using their 3D tissue printers, will offer a more realistic replica of the tumor microenvironment than traditional tissue culture and provide more human qualities than would be possible with mouse models.
Many anticancer drugs fail in clinical trials despite promising early data in vitro and in mouse models. Eric David, MD, JD, Organovo chief strategy officer, notes that the anticancer drug evaluation guidelines released by the European Medicines Agency in January name the lack of nonclinical models with good predictive properties as “the greatest hurdle for efficient drug development within the foreseeable future.” The company and OHSU hope 3D tumors made in vitro will be better models.
Organovo's system uses 2 print heads, with one depositing clusters of cells while the other lays down a supportive gel that gives the new tissue its form and is removed shortly after printing. A computer interface allows the user to control the tissue design, working in 3 dimensions to make complex structures, switching between “inks” containing different types of cells as needed. After a few days, the cells begin to fuse together and do the work of setting up their microenvironment.
“We rely on the native ability of cells to self-assemble,” says David. The company sells the assembled tissues, including blood vessels, lung, liver, and muscle.
The OHSU group will work with the Organovo printers to develop tumor models, starting with recent patient samples of breast and pancreatic cancer. Joseph Carroll, PhD, the associate director of business development at Knight Cancer Institute, says the resulting models will be used for drug development and to study phenomena such as cancer stem cell behavior.
To sell cancer researchers on the new models, Organovo will have to clear a high bar by showing that its models can mimic cell signaling and other features of tissues in a similar manner to in vivo models. If such characteristics can be replicated in a 3D model that lasts over months and years, like real tumors, “I'd be pretty psyched,” says Jonathan Kurie, MD, an oncologist at The University of Texas MD Anderson Cancer Center in Houston.
“Mouse models are very expensive and slow, but they give you the ability to watch tumors develop over time,” Kurie points out.
Carroll says he hopes the 3D tumor models will last over the course of weeks, but it's not possible to say until they are actually built.
Zev Gartner, PhD, a professor of pharmaceutical chemistry at the University of California, San Francisco, who is working on in vitro 3D models of mammary tissue, says the best test of the Organovo tumors would be to use them to screen cancer drugs that appeared promising in preclinical tests but subsequently failed in clinical trials. “Then you will really see if the new model is a better predictor,” Gartner remarks.
Such a test may be possible in 2 to 3 years, when the OHSU group hopes to begin drug screening.
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