URochester researchers hit an important FDA milestone for tissue chip technology that predicts dangerous immune reactions to cancer therapies.
Animal testing has long been the standard for evaluating new drugs before they reach human patients. But when it comes to cancer immunotherapy drugs, animal models often fail to predict which immunotherapies might produce harmful side effects in humans because they do not have the same responses or the same cell receptors. Researchers from the University of Rochester's Translational Center for Barrier Microphysiological Systems (TraCe-bMPS) are working on a high-tech solution: tissue chips, also known as organs-on-a-chip.
TraCe-bMPS is attempting to create drug discovery tools that could ultimately be accepted by the US Food and Drug Administration for use in evaluating new drugs. The tools are built using the modular, mass-producible µSiM chips with ultrathin membranes of human cells pioneered by center director James McGrath, the William R. Kenan, Jr. Professor of Biomedical Engineering. The platform also leverages sensors integrated directly into the chips, developed by Professor Benjamin Miller, that allow researchers to monitor barrier function and inflammatory signaling in real time.
Immunotherapies heighten the immune system's ability to detect and kill cancer cells. But they can produce adverse effects such as cytokine release syndrome (CRS)-an inflammatory response that can lead to organ failure-and immune effector cell-associated neurotoxicity syndrome (ICANS), which causes the immune cells to attack nerves.
"The goal is to predict these toxicities from human cells on a chip, before a drug ever reaches a patient, and to do it without relying on animal models that have repeatedly failed to predict CRS in people," says McGrath.
An important regulatory milestone
Previous studies have demonstrated the technology's promise, and the team recently overcame a significant hurdle by being accepted into the FDA's Innovative Science and Technology Approaches for New Drugs (ISTAND) pilot program, which helps evaluate new tools for developing drugs.
"We're excited the FDA sees value in developing tissue chips, and we will work hard to go through the remaining steps to ensure the research community can more widely leverage this technology for drug discovery," says Joan Adamo, director of regulatory support services at URochester Medicine's Clinical & Translational Science Institute.
The team is now working to submit a detailed qualification plan to the FDA with clinical considerations, timelines, data sharing plans, and the statistical methods that will be used to evaluate the tissue chip technology. They can then apply for full qualification. If the technology becomes FDA-qualified, companies could use it to have a more human-like way to test potential medicines and include those results when filing new drug applications with the FDA.
Beyond animal testing
The FDA began efforts to move away from animal testing with the FDA Modernization Act 2.0 in 2022, and the pace increased with the FDA's 2025 Roadmap to Reducing Animal Testing in Preclinical Safety Studies. While very few tissue chip systems have made it to this stage in the regulation process so far, Adamo says it is a rapidly changing field, and the demand for this technology is quickly growing.
"The FDA was very interested from the outset in making sure there will be companies that want to use this technology," says Adamo. "It has been easy to interest pharmaceutical companies in the development of this tool, as there are many immunotherapies in clinical trials that carry the risk of CRS and ICANS."
McGrath and Adamo say they collaborated closely with Graham Marsh '14 (PhD) from the nonprofit Critical Path Institute to submit the candidate drug discovery tool, and acknowledge Pfizer scientists for helpful discussions on the utility of the tool in drug development.
