G4S Antibodies Enable a New Breakthrough in CAR‑T Cell Function Research | Professor Huang He’s Team Publishes in Nature Cancer, Unveiling a Novel Mechanism Regulating Ferroptosis (IF: 28.5) Quality First, Innovation Driven
Release Date:
2026-06-22 15:48
Recently, Professor Huang He’s team at Zhejiang University published in the top oncology journal “…”. Nature Cancer 》published a research paper titled “Iron-mediated ferroptosis impairs CAR-T cell function and antitumor efficacy.” This study is the first to reveal that Serum iron overload By elucidating the key mechanisms by which ferroptosis induces functional exhaustion of CAR‑T cells, we have proposed a targeted approach. ACSL4 Alternatively, a novel strategy involves using the ferroptosis inhibitor Fer-1 to enhance CAR-T cell persistence and antitumor efficacy.
Paper Information
Title: Iron-mediated ferroptosis impairs CAR-T cell function and antitumor efficacy
Journal: Nature Cancer
Impact Factor: 28.5
Author’s affiliation: The First Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University Institute of Hematology
Publication Date: June 10, 2026
DOI: 10.1038/s43018-026-01187-2
Research Background
CAR‑T cell therapy has demonstrated remarkable efficacy in hematologic malignancies; however, its insufficient long-term persistence remains a critical bottleneck contributing to disease relapse. Although CAR‑T cells undergo rapid expansion following infusion, the underlying mechanisms of the subsequent “exhaustion phase” remain poorly understood. Ferroptosis, a form of iron‑dependent, lipid‑peroxidation‑driven programmed cell death, has not yet been validated in clinical samples as a factor contributing to CAR‑T cell functional exhaustion.
Research Content
The research team, through… Multiple myeloma and peripheral blood samples from patients with acute lymphoblastic leukemia following CAR‑T therapy, subjected to single‑cell transcriptomics, proteomics, and Metabolomics analysis , first discovered:
CAR‑T cells undergo ferroptosis after infusion: during the depletion phase, CAR‑T cells exhibit hallmark features of ferroptosis, including marked accumulation of lipid‑peroxidation‑derived reactive oxygen species, elevated intracellular ferrous iron levels, and downregulation of GPX4.
Iron overload in the serum is a driving factor: patients exhibit a significant increase in serum iron concentrations during the remission‑induction phase, and non‑responders have higher baseline ferritin and iron levels.
ACSL4 is a key regulatory node: iron promotes the phosphorylation of ACSL4, reshapes membrane lipid composition, increases the pool of polyunsaturated fatty acid–containing phospholipid substrates, and thereby drives lipid peroxidation.
Gene knockout of ACSL4 significantly enhances therapeutic efficacy: In mouse models of leukemia and osteosarcoma, CAR‑T cells with ACSL4 knocked out exhibit enhanced tumor‑clearing capacity and prolonged survival.
Research Innovation Points
New Clinical Findings
This study, based on clinical samples from patients with multiple myeloma and acute lymphoblastic leukemia, is the first to demonstrate in humans that ferroptosis occurs following CAR‑T cell infusion.
Mechanism in-depth elucidation
The system comprehensively elucidates the molecular signaling axis underlying iron‑induced ferroptosis in CAR‑T cells: iron overload triggers a massive accumulation of mitochondrial reactive oxygen species (ROS), which in turn activates the ACSL4 protein, ultimately initiating a robust lipid peroxidation cascade. This stepwise mechanism reveals the core molecular pathways through which iron mediates CAR‑T cell dysfunction and death.
Innovative therapeutic strategies
By comparing the advantages and disadvantages of different intervention strategies, we innovatively proposed an intrinsic ferroptosis‑regulating approach that targets CAR‑T cells themselves. Our findings demonstrate that this strategy offers superior safety and enhanced targeting specificity compared with systemic drug administration.
Key target validation
Functional validation targeting ACSL4 revealed that gene‑editing–mediated knockout of ACSL4 confers CAR‑T cells with a more durable and robust protection against ferroptosis than pharmacological preconditioning.
Significance and Prospects of the Study
This study addresses the industry’s central scientific challenge of the limited in vivo persistence of CAR‑T cells, while also identifying precise molecular targets for the next generation of engineered CAR‑T cells. The ACSL4‑knockout–based intervention strategy can be seamlessly integrated into existing CAR‑T cell manufacturing platforms, enhancing the cells’ intrinsic resilience to adverse in vivo microenvironments. Furthermore, the research demonstrates that patients’ baseline iron metabolism levels can serve as a novel biomarker, enabling the precise identification of individuals most likely to benefit from CAR‑T therapy and providing critical guidance for personalized clinical treatment.
G4S Antibody: A Core Detection Tool in CAR-T Research
Shanghai Hycells Biotechnology Co., Ltd. provided critical antibody support for the CAR‑T cell characterization and functional validation in this study. The anti‑G4S antibody used in the research (batch number: APS230402) is an in‑house‑developed product, employed in flow cytometry to assess CAR expression levels. With its outstanding specificity and sensitivity, it ensures the accuracy and reliability of the experimental data. Leveraging a mature recombinant antibody R&D platform and a stringent quality‑control system, Hycells has established a strong foothold in the cell‑therapy field, offering comprehensive antibody solutions to support the entire R&D and quality‑assurance process for CAR‑T and other cell‑therapy products.
Core Advantages of G4S Antibodies
Excellent versatility: Extensive experimental validation has demonstrated that it can serve as a universal CAR positivity‑rate assay reagent, streamlining the experimental workflow and shortening the R&D cycle.
Wide range of applications: Applicable to CAR assays for all target antigens (including (G4S)n, n≥2); applicable to CAR assays for different antibody types (including (G4S)n, n≥2).
Strong anti-interference capability: Effectively circumvents antigen interference, accurately restores the true CAR cell ratio, and yields more objective assay results.
Ultra-high sensitivity: It maintains stable and efficient detection performance across both high- and low-expression ranges of CAR, making it suitable for a wide variety of experimental settings.
In addition to antibody products, Hycells also offers a one-stop, end-to-end immune cell culture solution for cutting-edge cell therapy research. The company is dedicated to the R&D of primary cell technologies and, guided by a philosophy of full‑process optimization, has established an industry‑leading immune cell culture system. The comprehensive solution comprises six core modules. : Compliant seed cells, HiMag sorting kit, HiXpan ® Serum-free culture kit, HiXpan ® Platelet lysate, Cell Feeder bottom-permeable cell culture flasks, HiXpan ® Serum-free cell cryopreservation solution A full‑chain product portfolio has established a closed‑loop cell culture system, providing efficient, robust, and compliance‑aligned end-to-end technical support for both research and industrialization projects.
Information on Integrated Immune Cell Culture Products
Item number | Product Name |
hPB3T-10C-NS | Frozen hPB T cells Separate Service (NS), 10 million |
hPB4T-10C-PS | Frozen hPB CD4+ T cells Separate Service (PS), 10 million |
hPB8T-10C-PS | Frozen hPB CD8+ cells Separate Service (PS), 10 million |
MNC-h3NS100 | Human CD3 Negative Selection Magnetic Bead Kit |
MNC-h4PS100 | Human CD4 Positive Selection Magnetic Bead Kit |
MNC-h8PS100 | Human CD8+ Positive Magnetic Bead Isolation Kit |
HYS01002-kit | Human T Cell Activation and Expansion Kit (4×10 7 cells) |
HYS01016 | HiXpan ® Cell culture additives |
HYS-CF1000 | Cell Feeder Bottom-Permeable Cell Culture Flask |
HYS01013 | HiXpan ® Serum-free cell cryopreservation solution |
T-cell sample resources
The starting materials and core foundational components of the entire CAR‑T cell manufacturing process are peripheral blood mononuclear cells (PBMCs) or purified T cells isolated from healthy donors or patients, which serve as the material basis for all subsequent ex vivo manipulations.
T Cell Sorting Kit
It is used to efficiently isolate and purify target T cells from peripheral blood samples, yielding high-purity cell material and ensuring the quality of downstream experiments and preparations.
T-cell activation magnetic beads
The “initiator” of activation and proliferation signals, mimicking antigen-presenting cells through surface anti‑CD3/CD28 antibodies, delivers activating signals that trigger the critical transition of T cells from a quiescent state to activation and proliferation.
Platelet lysate
Cell culture supplements provide activated T cells with a variety of growth factors and nutrients, facilitating cell expansion and maintaining cellular physiological activity.
Cell Feeder Bottom-Permeable Cell Culture Flask
A “bioreactor” for cell expansion and maintenance, providing a long-term, stable in vitro culture environment for activated T cells.
Serum-free cell cryopreservation solution
A specialized reagent for cryopreservation of cells, designed to maximize the preservation of cellular structure and physiological function, maintain stable cell viability during freezing, and ensure high post-thaw survival rates and intact biological characteristics.
Hycells offers expert pre-sales consulting and after-sales support: one‑on‑one assistance to solve experimental challenges, timely delivery of the latest technical resources, and end-to-end guidance through product selection, hands-on implementation, and data analysis.
Related News
With the rapid advancement of cell and gene therapies, the industry is placing increasingly stringent demands on the performance, batch-to-batch consistency, and supply-chain reliability of cell-sorting reagents. At present, the domestic market for sorting magnetic beads remains dominated by imported brands, and their high cost of use and uncertain supply have become significant barriers to both research and industrialization in China.
Recently, Professor Huang He’s team at Zhejiang University published in the top oncology journal “…”. Nature Cancer 》published a research paper titled “Iron-mediated ferroptosis impairs CAR-T cell function and antitumor efficacy.” This study is the first to reveal that Serum iron overload By elucidating the key mechanisms by which ferroptosis induces functional exhaustion of CAR‑T cells, we have proposed a targeted approach. ACSL4 Alternatively, a novel strategy involves using the ferroptosis inhibitor Fer-1 to enhance CAR-T cell persistence and antitumor efficacy.
Hycells’s Selected PBMC Reconstruction Data Presentation (Part 2)
HuPBMC model Due to its rapid establishment (3–4 weeks) and ease of use, it has been widely employed for in vivo efficacy evaluation in tumor immunotherapy. However, the conventional model suffers from a critical limitation: the randomness and uncertainty inherent in donor selection. The root of the problem lies not in the model itself, but in the “seed” cells—PBMCs—introduced into the system.
Hycells’s Selected PBMC Reconstruction Data Presentation (Part 1)
The humanized PBMC-CDX model is an essential tool for in vivo efficacy evaluation of tumor immunotherapy agents. However, significant inter‑donor variability exists in the engraftment efficiency, T‑cell subset differentiation, and the risk of graft‑versus‑host disease (GVHD) among different PBMC donors, which directly impacts model stability and the experimental window.
A Fresh Start, A New Beginning | Hycells’s Brand Identity Fully Reimagined
Every step forward is aimed at fulfilling our mission even more effectively.
Focused on peptide immunogenicity assessment, precisely empowering tumor neoantigens.
In the field of cancer immunotherapy, tumor neoantigen–specific T-cell responses serve as a key metric for assessing peptide immunogenicity. Leveraging its well-established in vitro assay platform, Hycells Biotechnology offers end-to-end services—ranging from initial screening of peptide immunogenicity and antigen‑specific T-cell expansion to validation of tumor cell‑killing activity—thereby supporting the efficient and reliable discovery and validation of neoantigens.
Contact Us
Phone: 021-36696819
Mobile phone:13061948224(Ms. Yu)
Email:monika@hys-bio.com
Wuxi Headquarters: 4th Floor, No. 15-1, Xianfeng Middle Road, Anzhen Subdistrict, Xishan District, Wuxi City
Shanghai Branch: Room 503, Building 2, No. 999 Jiangyue Road, Minhang District, Shanghai
Official Website
WeChat Official Account
Message Board