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On September 9, 2022, Saiyuan Bio ("CellOrigin") announced that it had reached a global strategic cooperation agreement with Qilu Pharmaceutical to jointly develop, manufacture and commercialize an induction Pluripotent stem cells (iPSC) derived chimeric antigen receptor macrophages (CAR-iMACs) are used in cancer immunotherapy. This cooperation will give full play to the advantages of both parties, integrate complementary technologies and expertise, and combine industry-leading R&D, manufacturing and marketing capabilities . The two parties will cooperate in the development and commercialization of new drugs to jointly promote the CAR-iMAC pipeline to enter the clinical trial stage.
About Saiyuan Bio
Saiyuan Bio has long been focusing on iPSC-derived innate immune cells and its application in novel cancer immune cells. The company owns the proprietary technology of iPSC-derived CAR-Macrophage to fully unlock the potential of iPSC-derived immune cells . These cells are highly editable, scalable, and clonal. In response to factors that affect the effectiveness of macrophages (MACs) in vivo functions—phagocytosis, polarization, and chemotactics—Saiyuan Bio has conducted in-depth research and technical optimization through technical modules, and has accumulated improvements for different functions. The series of products has laid a solid foundation for subsequent product pipeline upgrades and clinical transformation, making it better used in tumor immunotherapy .
According to the official website data, Saiyuan Bio has established 6 R&D pipelines for hematoma and solid tumor , both in the preclinical stage. In July 2022, the company announced a new round of investment from Kunlun Capital to develop its current iPSC-derived innate immune cells, such as iPSC-CAR-Macrophage. Previously, Saiyuan Bio also received bio-VC investments from Shulan Health and Nest.
About CAR-iMACh
Tumor-related Macrophage is the core of immunosuppressive cells and cytokine networks and plays a crucial role in tumor immune evasion. Macrophages are divided into two main subpopulations, namely M1 and M2 macrophages. M1 macrophages are the first line of defense against microbial infection. M1 macrophages also maintain strong antigen presentation ability, inducing a strong Th1 response. In contrast, M2 macrophages play a key role in limiting the immune response, inducing angiogenesis , and tissue repair. Therefore, the presence of M2 macrophages is related to protumor activity, while the presence of M1 macrophages is related to antitumor activity.
Compared with immune cells such as T cells and NK cells, macrophages may be more likely to infiltrate tumors in an immunosuppressive microenvironment, providing new opportunities for tumor immunotherapy.
In 2016, experts from the University of Pennsylvania published a research paper, using CAR targeting HER2 to modify macrophages, and used mouse models to verify the good killing effect of CAR-iMAC (CAR-M) cells on tumors. It was also found that HER2-CAR-M can convert M2 macrophages into M1 macrophages, induce inflammatory tumor microenvironment, and enhance the anti-tumor cytotoxicity of T cells.
2020, experts from Zhejiang University reported for the first time the application of CAR-iMAC in anti-tumor immune cell therapy: iPSCs expressing CAR can differentiate into macrophage-like cells, and in the absence of antigen, CAR-iMAC is closer M2 polarization state; in the presence of specific antigens, CAR-mediated signaling promotes phagocytosis of CAR-iMACs and leads to the transformation of CAR-iMACs to proinflammatory M1 type. It is proved that iPSC-derived macrophages may become an important cellular source for myeloid tumor immunotherapy.
Compared with CAR-T, the advantages of CAR-iMAC include:
- CAR-iMAC can reduce the proportion of tumor-related macrophages, affect the cell phenotype of MAC, and have a positive effect on tumor treatment. In addition to phagocytosis of tumor cells,
- CAR-iMAC also promotes antigen presentation and enhances T cell killing. Compared with CAR-T,
- has limited circulation time and has less non-tumor targeting toxicity.
According to incomplete statistics, there are currently 13 CAR-iMACs under development. Among them, the clinical trials of two CAR-iMACs have been approved by the FDA, namely CARISMA's CT-0508, which are currently being developed for relapse/refractory treatment. Patients with HER2 overexpressing solid tumors; the other is MaxCyte's MCY-M11, which is currently being developed for recurrent/refractory peritoneal mesothelioma, ovarian cancer and other indications.
