A team of researchers led by NYU Tandon School of Engineering's Weiqiang Chen has developed a miniature device that could transform how blood cancer treatments are tested and tailored for patients.

The team’s microscope slide-sized "leukaemia-on-a-chip" is the first laboratory device to successfully combine both the physical structure of bone marrow and a functioning human immune system, an advance that could dramatically accelerate new immunotherapy development.

This innovation comes at a particularly timely moment, as the FDA recently announced a plan to phase out animal testing requirements for monoclonal antibodies and other drugs, releasing a comprehensive roadmap for reducing animal testing in preclinical safety studies.

As described in a paper published in Nature Biomedical Engineering, the new technology allows scientists to observe in real time how immunotherapy drugs interact with cancer cells in an environment that closely mimics the human body, representing exactly the type of alternative testing method the FDA is now encouraging.

"We can now watch cancer treatments unfold as they would in a patient, but under completely controlled conditions without animal experimentation," said Chen, professor of mechanical and aerospace engineering.

Chimaeric Antigen Receptor T-cell therapy, or CAR T-cell therapy, has emerged as a promising immunotherapy approach for treating certain blood cancers.

It involves removing a patient's immune cells, genetically engineering them to target cancer, and returning them to the patient's body.

Despite its potential, nearly half of patients relapse, and many experience serious side effects including cytokine release syndrome.

Scientists have struggled to improve these treatments, in part because conventional testing methods fall short.

Animal models are time-consuming and difficult to monitor (and fail to accurately mimic the human immune system's complex responses to these therapies), while standard laboratory tests do not represent the complex environment where cancer and immune cells interact.

The new device recreates three regions of bone marrow where leukaemia develops: blood vessels, surrounding marrow cavity, and outer bone lining.

When populated with patient bone marrow cells, the system begins to self-organise, with cells producing their own structural proteins like collagen, fibronectin, and laminin, creating not only the physical structure but, most importantly, retaining the complex immune environment of the tissue.

Using advanced imaging techniques, the researchers watched individual immune cells as they moved through blood vessels, recognised cancer cells, and eliminated them, a process previously impossible to witness with such clarity in a living system.

The team could track precisely how fast the CAR T-cells travelled while hunting down cancer cells, revealing that these engineered immune cells move with purpose when searching for their targets, slowing down when they detect nearby cancer cells to engage and destroy them.

"We observed immune cells patrolling their environment, making contact with cancer cells, and killing them one by one," Chen said.

The researchers also discovered that engineered immune cells activate other immune cells not directly targeted by the therapy, a "bystander effect" that may contribute to both treatment effectiveness and side effects.

By manipulating the system, the team recreated common clinical scenarios seen in patients: complete remission, treatment resistance, and initial response followed by relapse.

Their testing revealed that newer "fouth-generation" CAR T-cells with enhanced design features performed better than standard versions, especially at lower doses.

While animal models require months of preparation, the leukaemia chip can be assembled in half a day and supports two-week experiments.

"This technology could eventually allow doctors to test a patient's cancer cells against different therapy designs before treatment begins," Chen explained.

"Instead of a one-size-fits-all approach, we could identify which specific treatment would work best for each patient."

The researchers developed a "matrix-based analytical and integrative index" to evaluate the performance of different CAR T-cell products, analysing multiple aspects of immune response in different scenarios.

This comprehensive analysis could provide a more accurate prediction of which therapies will succeed in patients.

Source: NYU Tandon School of Engineering