CAR-T immunotherapy has shown remarkable success in treating blood cancers, yet nearly 50% of patients experience relapse or severe side effects. Traditional 2D cell cultures and animal models fail to replicate human immune-microenvironment interactions, creating critical bottlenecks in therapy optimization 69. The leukemia chip solves this by engineering a functional 3D bone marrow analog on a microscope-slide-sized device, combining vascular, medullary cavity, and endosteal compartments with patient-derived stromal/immune cells 37.
Dynamic Microenvironment: Primary human bone marrow mononuclear cells self-assemble into collagen/fibronectin networks that maintain immune cell diversity (CD14⁺ monocytes, CD8⁺ T cells) for >9 days, achieving >90% structural similarity to human marrow 37.
Real-Time Battlefield Imaging: Advanced live-cell microscopy captured CAR-T cells patrolling marrow at 1.213 μm/min, forming immune synapses with cancer cells, and releasing perforin/granzyme B—the first direct observation of this process ex vivo37.
Clinical Scenario Simulation:
Remission: 10,000 CAR-T cells eliminated >99% leukemia cells in 7 days
Resistance: Low-dose CAR-T (2,500 cells) failed due to insufficient tumor penetration
Relapse: CD19-negative clones proliferated post-treatment (mimicking clinical recurrence) 17
CAR-T Design Optimization: Compared CD28ζ, ICOSζ, and 4-1BBζ CAR constructs, revealing cytokine secretion differences (IL-13 vs. IL-10) linked to side-effect risks 7.
Personalized Response Prediction: Tested CAR-T cells from 4 patients; only lung cancer patient-derived cells achieved remission, correlating with 4.7× higher cytokine secretion 37.
Manufacturing Breakthrough: Short-term cultured CAR-T (3-day) outperformed 9-day products in proliferation and cytotoxicity, potentially slashing production costs 3.
Regulatory Shift: Aligns with FDA’s 2025 roadmap to reduce animal testing; chip assembly takes 0.5 days versus months for animal models 26.
Precision Medicine Pipeline: Envisions patient-specific chips for pre-treatment screening—testing CAR-T designs/dosing before human infusion 910.
Economic Advantage: Cuts drug development timelines by 40% while reducing animal use by 70% 3.
"We now track cancer immunotherapy responses in a fully controlled, animal-free environment, opening safer and more effective directions for leukemia treatment."
— Prof. Weiqiang Chen, NYU Tandon School of Engineering