Chimeric antigen receptor T (CAR T) cell therapy represents a milestone in leukemia treatment. CAR T works by targeting specific antigens on leukemia cells by genetically engineering chimeric antigen receptors on the surface of a patient’s T cells, with the goal of identifying and eliminating specific antigens on leukemia cells.
However, clinical data show that more than 50% of patients eventually relapse after CAR T treatment. One of the main reasons is that leukemia cells may reduce or lose expression of target antigens under therapeutic pressure. When this happens, CAR T cells are unable to effectively recognize and eliminate leukemia cells.
Previous efforts to address this limitation have relied heavily on redesigning the CAR structure through additional genetic engineering, but this process is time-consuming, expensive, and technically complex.
Now, researchers at the Institute of Process Engineering (IPE), Chinese Academy of Sciences, have developed a biomimetic platform that significantly enhances CAR T cell therapy for relapsed and refractory leukemia without the need for genetic modification of CAR T cells.
strategy has been validated alive Multiple relapsed and refractory leukemia mouse models, and in vitro It was reported that a large number of patient-derived samples were used. cell March 9th.
Researchers collaborated with Pearl River Hospital and Blood Disease Research Institute Hospital to analyze numerous clinical samples. Their analysis revealed that CD71, a protein involved in transporting iron into cells, is highly expressed on leukemia cells across a variety of leukemia types and stages, as well as on autologous CAR T cells.
Based on this discovery, the researchers precisely controlled the solvent environment and assembly conditions to create a biomimetic ferritin aggregation cell engager (FACE), a molecular “bridge” that induces the ordered self-assembly of ferritin, CD71’s natural ligand, thereby strengthening the interface between CAR T cells and leukemia cells.
During CAR T cell preparation, FACE tightly binds to CD71 on the surface of CAR T cells. After injection, FACE on CAR T cells also binds to CD71 on leukemia cells. FACE strengthens the interaction by linking the two cell types, enhancing CAR T cell recognition and leukemia cell clearance.
In a leukemia patient-derived xenograft (PDX) model with normal antigen expression, FACE-CAR T cells achieved the same therapeutic efficacy as conventional CAR T cells using only one-fifth the cell dose, while significantly reducing the risk of cytokine release syndrome.
Even when leukemia antigen levels fell to less than 10% of normal (under conditions where conventional CAR T cells had little effect), FACE-CAR T cells were still able to effectively eliminate leukemia cells, achieving 100% survival in the PDX model.
The researchers also used the cage-like structure of ferritin to develop a drug-loaded FACE called FACED. FACED-CAR T cells effectively treated PDX models with up to 40% initial leukemic burden and low antigen expression. FACED-CAR T cells also eliminated antigen-negative leukemia cells, which are often the cause of relapse.
Our FACE platform is comprised of endogenous proteins and FDA-approved polymer derivatives that can be prepared in a simple and scalable process. 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 injection, without any additional genetic manipulation of CAR. ”
Professor WEI Wei, corresponding author of the IPE study
Professor MA Guanghui from IPE said: “By systematically evaluating FACE across diverse patient-derived leukemia samples and clinically relevant PDX models, we demonstrated the broad applicability of FACE across disease subtypes and treatment resistance settings.” The researchers also established an efficacy database and developed an AI-assisted prediction framework that can accurately predict FACE-mediated enhancement.
Reviewer: cell He said the discovery was “highly relevant to the CAR T field” and a “promising translational approach” to improve responsiveness in hematological malignancies. They emphasized that this strategy does not require any additional genetic engineering, so it can be implemented in a variety of clinical settings, and it has the potential to counteract leukemia antigen heterogeneity.
In summary, this study presents a biomimetic platform that enhances CAR T cell performance through improved cell binding and targeted drug delivery. This strategy is supported by strong preclinical validation and provides a practical approach to improve outcomes in relapsed and refractory leukemia.
sauce:
Chinese Academy of Sciences
Reference magazines:
Lee, F. others. (2026). Ferritin aggregate cell engager for CAR T avidity engineering for refractory leukemia. cell. DOI: 10.1016/j.cell.2026.02.005. https://www.cell.com/cell/abstract/S0092-8674(26)00170-4
