The ‘real thing’ in cancer modeling

GAITHERSBURG, Md.—Trevigen Inc. has been awarded $252,000 for the Small Business Innovation Research (SBIR) Phase 1 Contract 261201300042C from the National Cancer Institute and the National Institutes of Health (NIH), to develop a tumor-aligned 3D coculture system. The objective, according to Dr. Gabriel Benton, the principal investigator, is to “develop a high-throughput, 3D coculture that exhibits tumor physiology as it exists in the real world to be able to predict the drug response.”

“When developing drugs to treat cancer, you can’t grow cells on plastic dishes and recapitulate the physiology,” explains Jay George, Trevigen’s chief technology officer. “The cells and culture have to be grown in 3D, because the drug reactions will require other cells to be present.”

According to Dr. Hynda Kleinman, a former NIH principal investigator, “Many anticancer drugs fail in human trials despite showing efficacy in in-vitro studies and animal models. It has become clear that 2D in-vitro monoculture assays do not reflect the complex cellular composition and microenvironment of the tumor tissue, and this may explain their failure to predict clinical efficacy.”

The goal of this NIH-funded contract is to develop an in-vitro tumor-aligned 3D culture model representative of the human tumor tissue architecture using breast cancer, stromal and endothelial cells and test this model with known effective anticancer drugs. The first objective of the contract is to optimize the composition of the extracellular matrix and the cell model to elicit physiological tumor morphology and behavior. The second objective is to characterize changes in gene expression for this model, comparing it with traditional 2D and 3D culture models. The final objective is to validate the model as effective by evaluating its physiological properties in response to anti-cancer drug treatments. Phase 2 will be worth $1.5 million.

“As to commercial potential, it is accepted by everyone that anticancer drugs take too long and cost too much to develop,” says Michael Elliott, president of Trevigen, which was founded in 1992 to provide reagents and kits for researchers investigating programmed cell death and DNA damage and repair.

With increased attention being placed on cell death and its role in cancer research, Trevigen has developed assays for cancer cell function and behavior, including angiogenesism cell invasion and tumor formation. The company develops and delivers technologies and systems for the study of cancer, drug development, regenerative medicine and translational research. Its objective is to provide researchers with assays that are innovative and more physiologically relevant.

“Forbes magazine estimated that it takes $5 billion to bring a drug to market,” Elliott notes. “When you remove the tumor material from the patient and grow it in labware, with the physiological environment taken away, you don’t have the same reaction as in the body. That gives you false data, which is not an efficacious situation.”

Trevigen, Elliott explains, provides cultures that mimic the environment of the tumor in the body. “By using our knowledge to mimic the body’s environment, we boost the ability to develop a better product system. Successful implementation of this model would save significant cost and time for drug development, ultimately benefiting the patient and society.”

“The models we develop help drug companies to find the appropriate anticancer drugs more efficiently and inexpensively,” George echoes. “False positives are expensive. If you’re going to fail, you want to fail fast and fail cheap and then move on to a compound that works. Additionally, taxpayers won’t have the burden of costly federal programs that don’t produce results, and the healthcare system and the people who use it will be the big winners. It will be good for the whole community.”