Engineered chip mimics bone marrow and immune system, offering a faster, tailored path for cancer immunotherapy.
A credit-card-sized chip may soon outsmart cancer.A team led by NYU Tandon School of Engineering’s Weiqiang Chen has developed a miniature device that could reshape how blood cancer treatments are tested and personalized.
Roughly the size of a microscope slide, the “leukemia-on-a-chip” is the first lab-grown system to replicate both the structural makeup of bone marrow and a functioning human immune response, marking a potential leap forward in immunotherapy research.The breakthrough comes as the FDA lays out plans to phase out animal testing for monoclonal antibodies and other drugs, outlining a roadmap for alternative safety testing.Where cancer meets precisionThis chip-based platform delivers just that, allowing scientists to watch in real time as immunotherapy drugs interact with cancer cells in an environment that closely mirrors the human body.“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.Chimeric Antigen Receptor T-cell therapy, or CAR T-cell therapy, has emerged as a powerful immunotherapy for certain blood cancers. The approach involves extracting a patient’s immune cells, genetically reprogramming them to attack cancer, and infusing them back into the body. Yet despite its promise, nearly half of patients eventually relapse, and many suffer serious side effects like cytokine release syndrome.One major obstacle to improving these therapies is the lack of effective testing systems. Animal models are slow, difficult to monitor, and poorly reflect the human immune system’s complexity. Standard lab tests, meanwhile, fail to capture the intricate cellular environment where cancer and immune cells interact.Cells in real timeThe new chip-based device changes that. It mimics the three key regions of bone marrow where leukemia takes hold—blood vessels, the surrounding marrow cavity, and the outer bone lining. When seeded with patient-derived bone marrow cells, the system begins to self-assemble, with cells generating their own structural proteins—collagen, fibronectin, laminin—and, crucially, sustaining a functional immune environment.Using high-resolution imaging, the researchers tracked immune cells in real time as they navigated blood vessels, identified cancer cells, and destroyed them, offering an unprecedented window into CAR T-cell behavior.The team observed that the engineered cells move with clear intent, accelerating through healthy tissue and decelerating near cancer cells as they zero in and eliminate their targets.“We observed immune cells patrolling their environment, making contact with cancer cells, and killing them one by one,” Chen said.The researchers also uncovered a surprising “bystander effect,” where engineered immune cells activated other immune cells not directly targeted by the therapy—a phenomenon that could enhance both treatment efficacy and side effects.By tweaking conditions within the chip, the team was able to simulate real-world clinical outcomes, including complete remission, treatment resistance, and relapse after an initial response. In these tests, newly developed “fourth-generation” CAR T-cells—with advanced design enhancements—outperformed standard versions, particularly at lower doses.Unlike animal models, which can take months to prepare, the leukemia chip can be assembled in just half a day and enables experiments over a two-week period, offering speed, precision, and scalability.“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.”To assess the effectiveness of different CAR T-cell therapies, the researchers created a “matrix-based analytical and integrative index” that evaluates multiple aspects of immune response across various clinical scenarios. This comprehensive framework could offer more accurate predictions of which therapies are most likely to succeed in patients.The full findings are detailed in a paper published in Nature Biomedical Engineering.
Bone Marrow Model Cancer Research CAR T-Cell Therapy Immune Response Immunotherapy Leukemia-On-A-Chip NYU Tandon Personalized Medicine Weiqiang Chen
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