Organ-on-a-chip technology could eradicate animal testing

Researchers at the University of Rochester are developing an organ-on-a-chip platform designed to improve the prediction of dangerous side effects from cancer immunotherapies.

The work, led by the university’s Translational Center for Barrier Microphysiological Systems (TraCe-bMPS), aims to provide drug developers with human-based testing tools that could eventually support regulatory submissions to the US Food and Drug Administration (FDA).

The team is using tissue chips containing human cells to investigate adverse immune reactions that conventional animal models can struggle to reproduce.

The technology combines modular µSiM chips, developed by the Center’s director James McGrath, with integrated sensors developed by Benjamin Miller to measure barrier function and inflammatory signalling in real time.

The project has reached an important regulatory milestone after being accepted into the FDA’s Innovative Science and Technology Approaches for New Drugs (ISTAND) programme.

The programme is intended to help assess innovative drug development tools for potential regulatory use.

If the Rochester platform ultimately achieves FDA qualification, pharmaceutical companies could use its data alongside other evidence when developing and seeking approval for new medicines.

Why cancer immunotherapy is difficult to test

Cancer immunotherapies work by strengthening the immune system’s ability to recognise and destroy cancer cells. However, stimulating the immune system can also trigger severe toxicities.

Two particularly serious complications are cytokine release syndrome (CRS), in which excessive immune activation causes widespread inflammation that can progress to organ failure, and immune effector cell-associated neurotoxicity syndrome (ICANS), which can affect the nervous system.

Animal studies do not always reproduce these human-specific immune responses. Differences in cell receptors and immune biology can therefore make it difficult to predict how a treatment will behave in patients.

An organ-on-a-chip offers a different approach by recreating aspects of human tissue using human cells within a controlled microfluidic environment.

This can allow researchers to observe biological responses that may be missed when testing across species.

Sensors provide real-time data

TraCe-bMPS is building its platform around µSiM chips containing extremely thin membranes made with human cells.

Sensors embedded directly into the devices can continuously monitor changes in tissue barrier integrity and inflammatory activity. That real-time capability could be particularly valuable when studying immunotherapies.

Rather than relying solely on an end-point measurement, researchers can track how tissues respond as immune activity develops, potentially revealing early warning signals of toxicity.

The broader FDA strategy increasingly recognises the potential of these human-relevant technologies.

Its current New Approach Methodologies framework includes organ-on-a-chip systems, organoids, computational models and other approaches intended to improve the relevance of preclinical testing.

From research platform to regulatory tool

The Rochester team’s acceptance into ISTAND does not mean the technology has been approved for routine drug testing.

Instead, it provides a pathway for working with regulators to establish whether the platform can generate sufficiently reliable and reproducible evidence.

The next stage is to submit a detailed qualification plan covering clinical considerations, timelines, data-sharing arrangements and statistical methods for evaluating the technology. Successful completion could eventually lead to full qualification.

That process is becoming increasingly relevant as the FDA moves to reduce reliance on animal testing.

In April 2025, the agency published a roadmap promoting human-relevant methods, including organ-on-a-chip systems, while in 2026 it issued draft guidance outlining how New Approach Methodologies can be validated for use in drug development.

For cancer drug developers, the potential is significant. A validated organ-on-a-chip could provide a more human-relevant way to investigate immune-related toxicity before a therapy reaches clinical trials, helping researchers identify risks earlier while reducing dependence on animal models.