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Poster 4556: Disrupting the CD47-SIRPa Anti-Phagocytic Axis in I/O

Phagocytosis Response of Macrophages to the CD47 Expression of Tumor Cells in Anti-CD47 Therapy

Huajun Yang, Zhongliang Li, Beibei Tang, Phillip Wang, Qinyun Ma, Frank Xing, and Qian Shi

CrownBio 2018. Poster 4556: Disrupting the CD47-SIRPa Anti-Phagocytic Axis in I/OMacrophages provide an important surveillance system, which can be escaped by human tumors expressing CD47. Reinstating macrophage functionality for clearing tumor cells, by targeting CD47 and thereby blocking the phagocytosis inhibitory CD47-SIRPalpha interaction, has therefore become an important strategy in immunotherapy.

CrownBio has developed a robust and reproducible in vitro assay platform to support preclinical anti-CD47 drug research. The technique applies a macrophage differentiation system using isolated CD14+ monocytes as starting material, and is able to achieve greater than 80% of M1 and M2 populations throughout a 6 day differentiation period.

This poster details initial in vitro findings, as well as validating the data in vivo via paired isogenic cell models in which the CD47 gene is knocked out in one sub-cell line and overexpressed in a second sub-cell line.

Read this Poster to Discover:

  • That CD47 expression level varies in different cancer cell models, with Karpas299 being a valid alternative to SK-OV-3 in phagocytosis studies, through expressing more CD47 and inducing more robust target engulfing activity
  • That M1 and M2 macrophages demonstrate comparable anti-CD47 antibody specific phagocytic activity, while anti-CD274 (PD-L1) treatment yields phagocytic activity comparable with isotype controls
  • The strong positive correlations between phagocytic activity and CD47 expression level in parental and derived isogenic models

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