Creating realistic systems

CHARLOTTESVILLE, Va.—“Researchers can take primary cells from specific human organs, but they die in the Petri dish, and trying to get a drug response is unrealistic,” explains Dr. Brian Wamhoff, vice president of research and development and co-founder of HemoShear, adding, “Drug discovery with cells on the bench is not meaningful in a human context. Tumor cells grow faster in a Petri dish than they do in humans, and other parameters are not the same as they are in the human body. Experimenting on mice is not the same as using the same drugs on humans.”

HemoShear, Wamhoff says, can create human responsiveness on the bench by taking multiple cell types that require each other in vivo, bringing them together in the right context and exposing them to physiological parameters that they experience in the human body. “The cells stay alive, wake up and respond, leading to better drug discovery,” he explains.

Funded by a contract with the National Cancer Institute (NCI), HemoShear is developing a series of tumor models that recreate a wide variety of cancers for discovery of new drugs. The company recently announced that it has completed the first phase of development of a novel cancer drug discovery platform that replicates human tumor biology and responds to clinically relevant drug concentrations. Using its new platform, HemoShear was able to successfully replicate human therapeutic response to cisplatin, a drug approved to treat non-small cell lung cancer (NSCLC), at a therapeutically relevant concentration. Similarly, HemoShear evaluated two other drugs currently in clinical studies and confirmed a therapeutic response.

When evaluated in traditional cell culture systems and mouse studies, the same dose of cisplatin does not show a response. HemoShear’s findings reinforce the need to test cancer drug candidates under more human-relevant tumor conditions.

“Nearly 95 percent of all cancer drugs entering clinical trials fail because of toxicity or lack of efficacy,” Wamhoff says. “A major contributor to this dismal failure rate can be attributed to the inability of traditional models to uncover the underlying disease biology and predict efficacy and safety of cancer drug candidates. With our novel approach to recreating the tumor microenvironment, we have demonstrated a major step toward understanding human response to cancer drug treatments.”

Wamhoff adds, “There are a lot of 3D tumor systems available, but ours can separate cell types to see how a drug targets each one. It’s a depth of biology not available on other systems.”

HemoShear started in 2008 with the goal of validating human responses to 200 drugs in order to enter drug discovery collaborations with select pharmaceutical and biotechnology companies to identify novel therapeutic approaches. By bringing together cancer cells, stromal cells and vasculature under the right conditions, the company hopes to improve the success of drug candidates when they enter the clinic and bring them to patients faster.

Two years ago, the NCI approached HemoShear to create its tumor microenvironment. The company has received more than $10 million in Small Business Innovation Research funding from the government.

HemoShear’s translational tissue systems apply physiological blood flow characteristics to human tissue to restore its in-vivo biology, using material from HemoShear’s biorepository and interpreting data with cutting-edge computational analytics. In Phase 1 of the NCI-funded program, HemoShear demonstrated that NSCLC tumor structure, biology and molecular signaling pathways are restored in the HemoShear platform.

“Now the company is about a half-year away from more robustly establishing a model for NSCLC and developing one for pancreatic cancer, then one for prostate cancer and, eventually, one for any solid tumor,” says Dr. Dan Gioeli, director of tumor studies at HemoShear. “We also want to create a model to analyze the mechanism of liver cancer, the most common site for metastasis of lung and pancreatic cancer. We’re trying to understand the biology of metastasis, so we can develop drugs to target it. We want to determine how drugs affect metastasis, how metastasis affects the site and how drugs interdict those processes.”

He concludes, “HemoShear’s goal is to enter drug discovery collaborations with select pharmaceutical and biotechnology companies to identify novel therapeutic approaches. We need to have the right partners, and we’re cautiously optimistic.”