While these results are promising in the laboratory, the next step is to test whether these reprogrammed macrophages can recognize and fight cancers in living animals.Ĭhimeric antigen receptors (CARs) are synthetic transmembrane receptors that redirect T cell activity towards clinically relevant targets (reviewed in ). The modified macrophages could also limit the growth of live cancer cells in a dish by ‘biting’ and even ‘eating’ them. These cells were then able to recognize and attack beads covered in proteins found on cancer cells. created a new type of CARs, named CAR-P, and introduced it in macrophages. Would it then be possible to use CARs to program macrophages to ‘eat’ cancer cells? They defend our body by ‘swallowing’ harmful cells. Macrophages are a group of immune cells that can make their way inside tumors and travel to cancers that the rest of the immune system cannot reach. Yet, these immune cells are not good at penetrating a solid tumor to kill the cells inside, which limits their use. T cells that carry CARs are already used to treat people with blood cancers. These receptors tell immune cells, such as T cells, to attack cancers. However, cancer cells often find ways to ‘hide’ from our immune system.Ĭhimeric antigen receptors, or CARs, are receptors designed in a laboratory to attach to specific proteins that are found on a cancer cell. It can spot these threats because it recognizes certain signals at the surface of dangerous cells. Our immune system constantly patrols our body, looking to eliminate cancerous cells and harmful microbes. Finally, we show that CAR-P expressing murine macrophages reduce cancer cell number in co-culture by over 40%. Addition of a tandem PI3K recruitment domain increased cancer cell engulfment. We show that CAR-Ps drive specific engulfment of antigen-coated synthetic particles and whole human cancer cells. By screening a panel of engulfment receptor intracellular domains, we found that the cytosolic domains from Megf10 and FcRɣ robustly triggered engulfment independently of their native extracellular domain. CAR-Ps consist of an extracellular antibody fragment, which can be modified to direct CAR-P activity towards specific antigens.
Here, we engineered a family of Chimeric Antigen Receptors for Phagocytosis (CAR-Ps) that direct macrophages to engulf specific targets, including cancer cells.
The success of CAR-T cell therapies highlights the promise of programmed immunity and suggests that applying CAR strategies to other immune cell lineages may be beneficial. Chimeric antigen receptors (CARs) are synthetic receptors that reprogram T cells to kill cancer.
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