Abstract B002: CD47 expression predicts efficacy of macrophage-mediated phagocytosis of tumor cells

Most human cancers express CD47 to escape the macrophage surveillance. To reinstate macrophage functionality in clearing tumor cells, targeting CD47 has been an important strategy in immune-oncology therapy. We profiled a large panel of tumor cell lines of both solid and blood tumors that are frequently used in cancer drug research and in Mixeno® animal study in Crown Bioscience for CD47. Despite its being reported as a ubiquitously expressed immune-escape marker in cancer cells, the expression levels of CD47 vary among different tumor cell lines when the cells were examined by flow cytometry. It is of interest that a portion of tumor cells in fact do not present CD47 despite gene expression data, such as RNA-seq data, suggesting that they do. To establish a robust and reproducible in vitro assay platform to support anti-CD47 drug research, we applied a macrophage differentiation system using isolated CD14+ monocytes as starting material, and were able to achieve > 80% of M1 and M2 populations, respectively, through the 6-day differentiation. Differentiated macrophage was cocultured with target tumor cells labeled for flow cytometry analysis. In the presence of anti-CD47 antibody, steady phagocytosis effect was observed with aCD47 BRIC126 antibody and target tumor cells expressing high level of CD47 markers. BRIC126 antibody blocks the CD47-SIRPalpha interaction. To prove the finding, we constructed isogenic cell models from the same parental cells in that CD47 gene is knocked out in one sub-cell line and overexpressed in another sub-cell line. The isogenic systems are also subject to the CD47 biology studies and can be served as positive and negative controls in phagocytosis assays. Detailed data will be discussed. Citation Format: Huajun Yang, Zhongliang Li, Beibei Tang, Frank Xing, Qian Shi. CD47 expression predicts efficacy of macrophage-mediated phagocytosis of tumor cells [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B002.