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Title

ANTI-CD47 ANTIBODY: A NEW HOPE FOR CANCER TREATMENT

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The efficiency and precision of cancer treatments, which may be surgical removal, radiotherapy, chemotherapy, or a combination of second and third depends upon the stage and type of cancer. Targeting CD47 and Signal inhibitory receptor alpha protein interactions (SIRPα) has evolved as one of several such methods of cancer therapy. Both CD47 and SIRPα belong to the Ig superfamily; CD47 is expressed by most cells, whereas SIRPα is restricted to neurons and myeloid lineage phagocytic cells, including macrophages. Interaction of SIRPα with growth factors, chemokines, or even induction from CD47 residing on the cell membrane of other cells results in phosphorylation at two out of four tyrosine residues at cytoplasmic domain. These phosphorylated regions serve as a docking site for the Src homology domain-containing phosphatases (SHP 1/2) that initiates signaling. This interaction has a roles in cell migration, cell proliferation, and, most notably, macrophage-mediated phagocytosis regulation (Figure 1). Studies have revealed that tumor cells show overexpression of CD47. It is one of the several tactics of immune evasion. Overexpression of CD47 on surface tumor cells blocks the FcꭚR mediated phagocytosis by macrophage. Even after opsonization by Ab (monoclonal Ab prepared against cancer antigen), tumor cells easily bypass macrophage-mediated phagocytosis through signaling phagocytes through CD47-SIRPα interaction. CD47-SIRPα interaction blocks myosin accumulation and FcꭚR aggregation at phagocytic synapse thus generating “do not eat me” signal which allow tumor cells to escape phagocytosis (Figure 2). Thus, this signaling principle has been exploited to block CD47 through anti-CD47 antibodies, thus making tumor cells more prone to macrophage-mediated phagocytosis.

Create Date

8/4/2024 2:35:05 PM

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