Chinese Team Pioneers "Nano-Armored" CAR-T Cell Therapy, Bringing Hope for Cure to Malignant Mesothelioma
Release time:
2025-11-21
Shanghai University-affiliated Mengchao Tumor Hospital recently announced a major breakthrough in a groundbreaking global study conducted in collaboration with top domestic research institutions, including the Shanghai Cell Therapy Group and the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences. By equipping CAR-T cells with "nano-armor," the study successfully treated malignant mesothelioma and, for the first time, demonstrated that this innovative therapy can provide significant clinical benefits to patients.
Malignant mesothelioma is a malignant tumor originating from the mesothelial tissues of body cavities, with approximately 85% of cases occurring in the pleura. It is characterized by high malignancy and strong invasiveness. Clinical data show that after the failure of standard treatments, the effectiveness of subsequent therapies is less than 30%, the disease control rate is below 70%, and the one-year survival rate is even lower than 50%. There is an urgent need for new treatment options.
In this study, published in Advanced Science, the research team pioneered the development of "Nano-Antibody Armored CAR-T Cell (NAC-T)" therapy. In the first Phase I clinical trial, 11 patients with malignant mesothelioma who had failed standard treatments showed encouraging results: no severe toxic reactions occurred during the treatment; 63.6% of patients experienced significant tumor shrinkage, including one case of complete remission, six cases of partial remission, and four cases of stable disease, achieving an overall disease control rate of 100%. The median overall survival of the patients reached 25.6 months, significantly longer than the 11 months observed with existing second-line treatments. Particularly noteworthy is that one patient with complete remission has maintained tumor-free survival for over three and a half years (45.6 months).
The core innovation of this therapy lies in equipping CAR-T cells with both a "targeting system" and "nano-armor." The research team combined alpaca-derived anti-PD-1 nano-antibodies with a mesothelin (MSLN)-targeting CAR, enabling NAC-T cells to secrete large quantities of these nano-antibodies upon specific activation at the tumor site. These nano-antibodies not only precisely counteract the suppression of immune cells by the tumor microenvironment but also achieve a local concentration more than 6,500 times higher than traditional antibody forms. This effectively blocks 63.7% of T-cell inhibitory switches (PD-1 molecules), thereby activating endogenous anti-tumor immune responses.
While enhancing efficacy, the research team also developed a more efficient "Baize (BZ) transposon system" by modifying a zebrafish-derived gene transposon system, providing a safer tool for gene editing. This innovative combination not only breaks through the efficacy bottleneck of CAR-T therapy for solid tumors but also achieves significant progress in safety.
Industry experts believe that this study marks a critical breakthrough for China in the field of tumor immunotherapy. It provides important insights for CAR-T therapy to tackle other solid tumors, such as lung and liver cancer, and will elevate China's level of tumor immunotherapy to new heights.
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