Investigators have bioengineered an organotypic immunocompetent chip—a laboratory device that combines the physical structure of human leukemia bone marrow and a functioning immune system—to empower real-time spatiotemporal monitoring of CAR-T cell functionality for leukemias. The preclinical results of the chip’s development are published in Nature Biomedical Engineering.
The study authors hope that improved screening with this "leukemia chip" could help to improve CAR T-cell therapies for patients with leukemia and other hematologic malignancies.
“This device addresses a significant gap in preclinical research, offering an advanced tool for studying CAR T-cell therapy’s dynamic and multifaceted responses to leukemia,” stated co-senior author Saba Ghassemi, PhD, Research Assistant Professor of Pathology and Laboratory Medicine, Center for Cellular Immunotherapies, Penn Medicine. “Its ability to model these processes in real time opens the door for more accurate predictions of clinical outcomes, ultimately helping to refine treatments before they are tested in patients.”
“We can now watch cancer treatments unfold as they would in a patient, but under completely controlled conditions without animal experimentation,” added co-senior author Weiqiang Chen, PhD, Professor of Mechanical and Biomedical Engineering, NYU Tandon School of Engineering.
Study Methods and Rationale
Although CAR T-cell therapy has been very promising in the treatment of patients with hematologic malignancies, many patients still relapse after treatment or experience serious adverse effects, necessitating further modification of these agents, which is not fully possible with current testing methods.
Additionally, the FDA announced in April 2025, that they plan to phase out animal testing requirements for monoclonal antibodies and other drugs. As such, drug developers need new ways to ensure that their treatments are working effectively as intended.
The researchers created the leukemia chip as a new method for preclinical evaluation of a CAR T-cell therapy's functionality. The chip can track T-cell extravasation, recognition of leukemia, immune activation, and cytotoxicity.
The device models the blood vessels, marrow cavity, and outer bone lining that make up a human immune system, which is then populated with bone marrow cells of a patient with leukemia and exposed to CAR T-cell therapy.
“By mimicking the bone marrow stroma and immune niches in three dimensions, the device allows us to observe CAR T-cell behavior and efficacy in a setting that closely mirrors the complexities of a real human body,” Dr. Ghassemi explained. “It incorporates vascular networks to support realistic immune interactions, providing a level of precision and insight that traditional 2D cell culture models or animal studies cannot achieve.”
Reported Findings
In their report, the study authors used the bioengineered chip to model heterogeneous responses of remission, resistance, and relapse to CAR T-cell therapy and map out the factors that lead to each response.
“We observed immune cells patrolling their environment, making contact with cancer cells, and killing them one by one,” Dr. Chen said. They tracked the movement of immune cells via advanced imaging techniques.
The researchers analyzed the functional performance of various CAR designs and protocols, both systemically and multidimensionally, in healthy donors and patients with leukemia. They found that newer generations of CAR T-cell products performed better than earlier generation agents due to their enhanced design features, especially at lower doses.
Notably, the device is also able to assembled quickly and the experiments can also be conducted quickly and efficiently.
“This technology could eventually allow doctors to test a patient’s cancer cells against different therapy designs before treatment begins,” Dr. Chen explained. “Instead of a one-size-fits-all approach, we could identify which specific treatment would work best for each patient.”
“This work represents a true multidisciplinary collaboration, underscoring the importance of expertise across diverse fields,” added Dr. Ghassemi. “By combining bioengineering with immunology, we’ve created a coherent model that not only mirrors the complex interactions of CAR T cells within the human leukemia niche but also offers a tool to test interventional strategies and the corresponding responses over time, bringing us closer to personalized, precision therapies for leukemia and other cancers.”
Disclosure: For full disclosures of the study authors, visit nature.com.
