Leukemia-on-a-Chip: A New Era for CAR T-Cell Therapy
- Molly Li
- Aug 27
- 4 min read
Updated: Aug 29
In July 2025, the NIH announced it would no longer support grants focused solely on animal models, signaling a shift toward platforms that better reflect human biology.
This bold move signals a future where platforms more faithfully reflecting human biology will take center stage - a future already being innovated in Dr. Weiqiang Chen's lab at NYU Tandon. Here, researchers have unveiled a groundbreaking bioengineered "trial-on-a-chip" system for leukemia, precisely mimicking the complex bone marrow environment with its stromal, vascular, and immune niches, thereby enabling real-time, human-relevant testing of CAR T cell therapies.
Hope on the Horizon: Closing the Gap
CAR T therapy has been revolutionary for leukemia treatment, but it is not without its challenges. Approximately half of all patients experience relapse or develop resistance, and serious side effects like cytokine release syndrome (CRS) remain a significant concern. Traditional preclinical models, such as 2D cultures, organoids, or immunodeficient mice, often fail to replicate the complexity of human immune responses and the intricate bone marrow microenvironment. Chen's chip system addresses this critical gap, providing a preclinical tool that is both human-relevant and dynamic.
How the Chip Works: A Trial in Real Time
The team designed a 3D vascularized microfluidic chip seeded with patient-derived bone marrow, stromal, immune, and leukemia cells. This system replicates the spatial structure of bone marrow, creating a living model where scientists can directly observe CAR T cells as they exit tiny blood vessels, locate leukemia targets, form connections, and ultimately destroy the malignant cells. Unlike older models, the chip captures the spatiotemporal dynamics of the therapy, acting as a mini-clinical trial running under controlled conditions.
Using the chip, researchers were able to watch CAR T cells behaving like patrolling guards in the bone marrow. They observed the cells squeezing through vessels to attack leukemia one by one, allowing them to reproduce key clinical outcomes seen in patients, including full remission, treatment resistance, and post-response relapse.
The system also demonstrated that not all CAR T products are equal; cells from different donors and patients showed varying levels of strength. Interestingly, CAR T cells grown for only three days (instead of the standard nine) retained more of their neutralizing power. The chip also showed that a newer, fourth-generation version of CAR T cells, engineered with an immune-boosting molecule called IL-18, was better at controlling tumors by releasing more "signal proteins" to rally other immune cells.
Why It Matters for Patients - More Options, More Hope
This platform offers a powerful new way to test patient-specific CAR T cells before treatment begins, helping to predict likely outcomes and identify potential risks earlier. It can reduce the reliance on costly, time-consuming animal studies and accelerate the optimization of CAR T designs. Ultimately, this innovation sets the stage for more personalized and safer cancer immunotherapies, bringing new options to patients with greater speed and precision.
Looking Ahead
While challenges remain—including scaling the system and sourcing patient-specific stromal cells—this chip serves as a crucial proof of concept. It demonstrates how preclinical testing can be faster, more predictive, and more ethically sound. As the NIH and other organizations move to prioritize human-centric research, platforms like this leukemia-on-a-chip offer a promising alternative to traditional animal models, moving the field of immunotherapy toward a future that more faithfully echoes the human body.
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