Researchers from the Massachusetts Institute of Technology implanted a 3mm-long device that can hold 16 different drugs or drug combinations into tumors in cancerous mouse models. The device is able to release the drugs in regions of cancerous tissue that don’t overlap.
After 24 hours, the MIT researchers analyzed the tumor tissue for drug sensitivity through antibodies that can detect markers of cell death or proliferation. The team found that the local drug response was similar to what occurred after systemic injection.
Meanwhile, researchers at Fred Hutchinson Cancer Research Center and Presage Biosciences simultaneously compared the responses to multiple cancer drugs or drug combinations in tumors and found that another device in development could accurately predict systemic responses to the drugs.
Researchers say the Presage technology enables the placement of multiple columns of drugs for analysis directly into the tumor, which makes it possible to assess drug effects with multiple biomarkers and in multiple regions to capture the heterogeneity of response within the tumor.
The findings, published in the May issue of Science Translational Medicine, showed that in xenograft lymphoma models, the technology known as CIVO could use well-characterized anticancer agents to induce spatially defined cellular changes around sites of drug exposure, specific to the known mechanisms of action of each drug. The observed localized responses predicted responses to the same drugs systemically delivered in animals.
The researchers also said the CIVO technology intentionally bypasses bioavailability, biodistribution, metabolism, and excretion issues associated with systemic dosing, making it possible to focus on whether the drug engages its target, how cancer cells respond to target engagement, and whether the ultimate fate of the exposed cells indicates potential for a patient response.
“This analysis creates a comprehensive portrait of drug response that has never been seen before this early in the drug development process,” said Richard Klinghoffer, Chief Scientific Officer of Presage Biosciences. “Using this technology, we can assess how drugs, both as single agents and in combinations, impact the biology of tumor cells in the context of the native tumor microenvironment.”