Adding new dimensions

SAN DIEGO—Organovo Holdings Inc., a creator and manufacturerof functional, three-dimensional (3D) human tissues for medical research andtherapeutic applications, and the Knight Cancer Institute at Oregon Health& Science University (OHSU), a national leader in translational oncologyresearch, know there are limitations to studying cancer cells in animal modelsor in suspension, in terms of predicting how a drug will perform in humanclinical trials. That may explain why 80 percent of drugs that enter clinicaltrials fail to get patents.

The American Cancer Society estimates that 1.6 millionAmericans will be diagnosed with cancer and more than half a million people(580,000) will die of cancer in 2013. New technologies that can more accurately replicate human tissue, suchas tumors and malignant disease, are important for the discovery of noveltherapeutics and to deliver better medicines for patients.

After meeting at a Biotechnology Industry Organization (BIO)partnering conference in 2011 and seeing the potential for synergy, Organovoand OHSU formed a collaboration to develop more clinically predictive in-vitro 3D cancer models that willultimately advance discovery of novel cancer therapeutics. These 3D biologicalmodels are designed to show how cancer cells develop and migrate, in order todeliver better oncology therapies for patients.

OHSU's Knight Cancer Institute, a pioneer in personalizedcancer medicine, has helped to prove that it is possible to shut down cellsthat enable cancer to grow without harming healthy ones, helping to makeonce-fatal forms of the disease manageable and ushering in a new generation oftargeted cancer therapies. A National Cancer Institute-designated cancercenter, OHSU's institute offers new treatments and technologies as well ashundreds of research studies and clinical trials.

Organovo, which creates models of what researchers see inthe human body, is collaborating with pharmaceutical and academic partners todevelop human biological disease models in three dimensions. These 3D humantissues have the potential to accelerate the drug discovery process, enablingtreatments to be developed faster and at a lower cost.

According to Joseph Carroll, associate director at OHSUKnight Cancer Institute, which has been involved in leading-edge cancerresearch that has helped to develop such therapies as Novartis' Gleevec, "Testtube creations are not real, and animal tissue is not human tissue. We want toknow what the tumor really looks like, how cancer cell migration happens andwhat the metastatic process is, and we want to see it in the actualmicro-environment."

By applying breakthrough bioprinting technology, Organovodevelops 3D, architecturally correct human disease models to improve theunderstanding of drug toxicity and efficacy earlier in the drug developmentprocess, enabling safer, more effective therapies. The bioprinter can "put downcells layer by layer, put the right cell types in the right positions, enlargepieces of tissue to make them anatomically correct and show how cells interactin a 3D context as they would in the body," explains Keith Murphy, chairman andCEO of Organovo.

The two parties expect that it will take one to two years tobuild the models, and three years to screen the drugs on them. The focus,according to Carroll, will be on breast and pancreatic cancers. Architecturallycorrect structures based on actual patient tissues can be incorporated into themodels.

As Murphy explains, "We'll be looking at solid tumors andmetastatic events to see how they proceed and can be prevented. We hope to havecell assays in a few years to identify therapy candidates. We hope to have athird party, like a pharmaceutical company, to come in and develop a drug basedon the research."

"There is big commercial potential in looking at newtargets, discovering new targets and developing drugs that couldn't bedeveloped otherwise," Carroll says.

"The collaboration will be powerful in terms of identifyingtarget opportunities and new drug therapies that will help patients directlyand build new diagnostic assays," Murphy adds.

"We expect that this collaboration will transform the waycancer patients are treated," Carroll concludes. "Our passion is technologytransfer to effect change in patient care to get it to the clinic as soon aspossible."