Great News to kick off the new year 2024 for Leman Biotech!
On January 2, 2024, Prof. Li Tang and Dr. Yugang Guo, co-founders of Leman Biotech, published a paper in the top international academic journal Nature Biotechnology (IF=68), titled "IL-10-expressing CAR-T cells resist dysfunction and mediate durable clearance of solid tumors and metastases". The paper comprehensively reveals the preclinical research results of metabolically enhanced Meta 10 CAR-T therapy for solid tumors. The relevant findings suggest that Meta 10 CAR-T has enormous potential for curing solid tumors.
CAR-T cell therapy has achieved tremendous success in the field of hematologic malignancies. However, there are still many technical bottlenecks and challenges in clinical applications, leading to a relatively low complete remission rate for some blood tumors and high recurrence rates. In particular, the therapeutic effects on solid tumors are very weak, and clinical cures are rare. One of the bottleneck reasons for CAR-T cell therapy in solid tumors is T cell exhaustion leading to T cell dysfunction.
Based on Leman Biotech's core technology of IL-10-mediated metabolic reprogramming (Meta 10), Prof. Li Tang and Dr. Yugang Guo, co-founders of Leman Biotech, collaborated with Dr. Jie Sun from Zhejiang University School of Medicine. They published a paper in the journal Nature Biotechnology titled "IL-10-expressing CAR-T cells resist dysfunction and mediate durable clearance of solid tumors and metastases". The research was specifically reported by Research Briefing - Nature Biotechnology (https://www.nature.com/articles/s41587-023-02061-7).
The study found that IL-10 self-secreting CAR-T cells (metabolically enhanced IL-10 CAR-T cells) can maintain the integrity of mitochondrial structure and function in the tumor microenvironment. They enhance oxidative phosphorylation metabolism in a manner dependent on mitochondrial pyruvate carrier (MPC). The expression of IL-10 promotes the proliferation and effector function of CAR-T cells, leading to complete regression of in situ solid tumors or metastatic solid tumors in multiple tumor models, including melanoma, breast cancer lung metastasis, colon cancer subcutaneous tumor, and human pancreatic cancer NSG mouse in situ model. Importantly, metabolically enhanced IL-10 CAR-T cells can induce a stem cell-like immune memory response. Mice cured by metabolically enhanced IL-10 CAR-T cells can resist the inoculation of tumor cells for the second time, achieving persistent immune protection.
Based on this technology, Leman Biotech has developed the metabolically enhanced IL-10 CD19 CAR-T (Meta10-19 injection), which is currently undergoing clinical translational research. Clinical studies related to metabolically enhanced IL-10 CD19 CAR-T (NCT05715606, NCT05747157, NCT06120166) started in February 2023. These studies involve extremely low treatment doses (1% to 5% of the commercialized CD19 CAR-T dose) and have consecutively achieved complete remission in over ten patients with relapsed/refractory lymphoma or relapsed/refractory acute leukemia.
The treatment process is mild and controllable, with no apparent cytokine storms or neurotoxicity, common side effects of CAR-T therapy, observed in any of the treated patients during the treatment period. Metabolically enhanced IL-10 CD19 CAR-T is expected to provide a safer, more effective, and affordable treatment option for patients with relevant cancers.
