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Highlights
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First time demonstrating that CD47 blockade has anti-tumor effects against HCC.
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In vitro CD47 blockade results in increase in phagocytosis of HCC cells.
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In vivo CD47 blockade inhibits HCC tumor growth in hetero/orthotopic models.
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CD47mAb400 is clearly more efficacious than widely-investigated B6H12 antibody.
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.
Via Krishan Maggon
Cancer Letters
Volume 360, Issue 2, 1 May 2015, Pages 302–309
Original Articles Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinomaZhenyu Xiaoa, 1, Haniee Chunga, 1, Babak Banana, Pamela T. Manningb, Katherine C. Otta, Shin Linc,Benjamin J. Capocciaa, Vijay Subramaniana, Ronald R. Hiebschb, Gundumi A. Upadhyaa, Thalachallour Mohanakumara, e, William A. Frazierd, Yiing Lina, , , William C. Chapmana, , doi:10.1016/j.canlet.2015.02.036
Volume 360, Issue 2, 1 May 2015, Pages 302–309
Original Articles Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinomaZhenyu Xiaoa, 1, Haniee Chunga, 1, Babak Banana, Pamela T. Manningb, Katherine C. Otta, Shin Linc,Benjamin J. Capocciaa, Vijay Subramaniana, Ronald R. Hiebschb, Gundumi A. Upadhyaa, Thalachallour Mohanakumara, e, William A. Frazierd, Yiing Lina, , , William C. Chapmana, , doi:10.1016/j.canlet.2015.02.036