Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma

Zhenyu Xiao, Haniee Chung, Babak Banan, Pamela T. Manning, Katherine C. Ott, Shin Lin, Benjamin J. Capoccia, Vijay Subramanian, Ronald R. Hiebsch, Gundumi A. Upadhya, Thalachallour Mohanakumar, William A. Frazier, Yiing Lin, William C. Chapman

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival times. The efficacy of current systemic therapies for HCC is limited. In this study, we used xenograft tumor models to investigate the use of antibodies that block CD47 and inhibit HCC tumor growth. Immunostaining of tumor tissue and HCC cell lines demonstrated CD47 over-expression in HCC as compared to normal hepatocytes. Macrophage phagocytosis of HCC cells was increased after treatment with CD47 antibodies (CD47mAbs) that block CD47 binding to SIRPα. Further, CD47 blockade inhibited tumor growth in both heterotopic and orthotopic models of HCC, and promoted the migration of macrophages into the tumor mass. Our results demonstrate that targeting CD47 by specific antibodies has potential immunotherapeutic efficacy in human HCC.

Original languageEnglish
Pages (from-to)302-309
Number of pages8
JournalCancer Letters
Volume360
Issue number2
DOIs
StatePublished - May 1 2015

Keywords

  • Antibody therapy
  • CD47
  • HCC
  • Xenograft models

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    Xiao, Z., Chung, H., Banan, B., Manning, P. T., Ott, K. C., Lin, S., Capoccia, B. J., Subramanian, V., Hiebsch, R. R., Upadhya, G. A., Mohanakumar, T., Frazier, W. A., Lin, Y., & Chapman, W. C. (2015). Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma. Cancer Letters, 360(2), 302-309. https://doi.org/10.1016/j.canlet.2015.02.036