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EXPLORE MORECreative Biolabs has a tradition of commitment. To achieve efficient execution and regulatory approval, we offer careful considerations of your program for the development of a cellular or gene therapy product – now and in the future.
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Given the current success of chimeric antigen receptor (CAR) T cell therapy and the potential for the development of CAR-natural killer cells, researchers have paid great interest in developing chimeric antigen receptor macrophage (CAR-MA) for tumor immunotherapy. Creative Biolabs is an emerging biotherapeutics company that is fully engaged in custom CAR-MA design & construction.
CAR-T cells have shown striking efficacy and are curative in hematologic malignancy. However, it is more challenging for the CAR-T cells to penetrate the tumor microenvironment and exhibit anti-tumor effect in the treatment of solid tumors. As a rapidly emerging treatment in the oncology field, CAR endows macrophages with the specificity of response against tumor-associated antigens (TAAs) in parallel with enhanced effector functions against the tumor. CAR-MA has the potential to address some challenges of CAR-T cells in the tumor microenvironment: immune cell penetration and immunosuppressive milieu.
The original structure of CAR was designed for T cells, but there is no CAR structure specifically for macrophages. We can consider adjusting the structure of CAR by associating different domains, to explore the most suitable CAR structure for macrophages to enhance the phagocytic effect of CAR-MA on cancer cells. In clinical applications, phagocytosis can be induced in macrophages by using first-generation CARs or monoclonal antibodies. To further enhance phagocytosis and increase macrophage activation, second/third generation CARs or bispecific antibodies that show dual specificity for tumor antigens or receptors on macrophages can be used. Similar to CAR-T cells, CAR for phagocytosis (CAR-P)-macrophages with the Megf10 or FcRγ intracellular region have been designed to engulf specific targets.
Fig. 1 Mediation and enhancement of tumor cell phagocytosis.1
Researchers have designed quite diverse CARs which can guide macrophages to devour specific targets. CAR-P, which expresses the intracellular domain of Megf10 or FcRv, promotes the phagocytic potential of target antigens. Adenovirus-induced CAR-MA using an anti-HER2 CAR containing the CD3ζ intracellular domain showed decreased tumor burden and prolonged overall survival in vivo. CAR-147 macrophages containing a single-strand antibody fragment targeting human HER2 and intracellular region of CD147 molecules significantly inhibited tumor growth in 4T1 breast cancer mouse models. Other attractive CAR-MA targets including CCR7, mesothelin, CD19, CD22 may help make these types of therapy available to a greater number of patients.
Fig. 2 The structures of various generations of CAR-MAs.2
Creative Biolabs is a biotech company developing a differentiated and proprietary cell therapy platform focused on engineered macrophages. Aiming at CAR-MA development, we provide custom CAR design and construction services. Please feel free to contact us for more details.
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CellRapeutics™ In Vivo Cell Engineering: One-stop in vivo T/B/NK cell and macrophage engineering services covering vectors construction to function verification.
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Canine CAR-T Therapy Development: From early target discovery, CAR design and construction, cell culture, and transfection, to in vitro and in vivo function validation.
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