Targeting CD47 pathway in tumor using the protein-siRNA conjugate
발표자
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초록
내용
Cellular “do not eat me” signal, CD47-SIRPa pathway, has been found as the one of the cancer cell immune evasion mechanisms as the downward signaling of the interaction blocks phagocytosis of the cancer cell by macrophages. By linking anti-CD47siRNA with the variant SIRPa protein, which blocks the binding, the conjugate demonstrates a dual mechanism of action in anticancer effect. First, the proteins bind to the CD47 receptor, and after subsequent endosomal uptake and escape, CD47siRNA completely silence the CD47 expression. Using the enzyme cleavable linker via maleimide-thiol reaction further facilitates the release of siRNA for the gene silencing. As a result, cancer treated with the conjugate was more readily phagocytosed compared to the control group. The conjugate group exhibited significant tumor size reduction and better accumulation in tumor cells compared to that of the PBS group and vSIRPa group in vivo. The study investigates the potential role of the conjugate vSIRPa-CD47siRNA and offers insight into cancer immune evasion via the CD47-SIRPa pathway.