New human tissue chips aim to replace animal testing

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.

James McGrath, the William R. Kenan, Jr. Professor of Biomedical EngineeringThe 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."

An important regulatory milestone

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.

Source:

University of Rochester