How could relapse in leukemia after CAR T treatment—a problem that still affects between 30–60% of patients—be prevented? One major driver is antigen escape: leukemia cells can dial down or lose the antigens that CAR T cells are engineered to recognize, effectively slipping into an invisibility cloak, known as antigen modulation. When that happens, even well‑designed CAR T cells struggle to find their targets.
While efforts to genetically re‑engineer CAR constructs continue, researchers at the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences have taken a different tack. They developed a biomimetic platform that boosts CAR T cell activity in relapsed and refractory leukemia without modifying the CAR itself. The work, published in Cell and titled “Ferritin aggregation cell engager for CAR T avidity engineering against refractory leukemias,” introduces a ferritin‑based molecular “bridge” that strengthens the physical and functional interface between CAR T cells and leukemia cells.
The team, working with Zhujiang Hospital and the Institute of Hematology & Blood Diseases Hospital, analyzed extensive clinical samples and found that CD71, a protein involved in iron transport, is highly expressed across leukemia types, disease stages, and even on autologous CAR T cells. That insight enabled them to design the ferritin aggregation cell engager (FACE) by precisely controlling ferritin self‑assembly under defined solvent and assembly conditions.
“FACE is composed of an endogenous protein and FDA‑approved polymer derivatives and can be prepared through a simple and scalable process,” said Wei Wei, PhD, corresponding author at IPE. “Importantly, it can be seamlessly integrated into existing CAR T cell manufacturing workflows as a culture supplement that is co‑incubated with CAR T cells prior to infusion, without any additional genetic engineering of CARs.”
FACE binds to CD71 on the T‑cell surface in CAR T cell preparation, and post-infusion, the same FACE molecules attach to CD71 on leukemia cells, creating a link between the two cell types. This link reinforces cell–cell engagement, enabling CAR T cells to better recognize and eliminate leukemia cells even when antigen levels are low.
FACE‑CAR T cells matched the efficacy of conventional CAR T cells using only one‑fifth of the cell dose in leukemia patient-derived xenograft (PDX) models with normal antigen expression, while reducing cytokine release syndrome risk. When antigen levels dropped below 10% of normal, FACE‑CAR T cells still cleared leukemia and achieved high survival in PDX models.
The researchers also extended the platform by loading ferritin’s cage‑like structure with chemotherapeutics, creating FACED. These drug‑loaded CAR T cells eliminated leukemia in PDX models with high initial tumor burden and low antigen expression and were able to target antigen‑negative leukemia cells that often drive relapse.
“By systematically evaluating FACE across diverse patient‑derived leukemia samples and clinically relevant PDX models, we demonstrated its broad applicability across disease subtypes and treatment‑resistant settings,” said Ma Guanghui, PhD, of IPE.
Beyond the biological validation, the team built an efficacy database and an AI‑assisted predictive framework to forecast FACE‑mediated enhancement across leukemia contexts.
“Building from our clinical insight that both diverse types of leukemia cells and corresponding CAR T cells strongly express CD71 (a ferritin receptor), we designed a ferritin aggregation cell engager (FACE) that can anchor to the CAR T cell surface, guide CAR T cells to face leukemia cells, and facilitate CAR recognition of cognate antigens,” the authors wrote. They added that this avidity‑engineering strategy offers a facile, universal, and flexible way to improve CAR T cell therapy for refractory leukemias—one that sidesteps the complexity of additional genetic engineering while directly addressing the challenge of antigen modulation.
The post CAR T Cell Therapy Boosted by Biomimetic Platform in Refractory Leukemia appeared first on GEN – Genetic Engineering and Biotechnology News.
