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

doi:10.1016/j.canlet.2015.02.036

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 journal › Article › peer-review

75 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 language	English (US)
Pages (from-to)	302-309
Number of pages	8
Journal	Cancer Letters
Volume	360
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2015.02.036
State	Published - May 1 2015
Externally published	Yes

Keywords

Antibody therapy
CD47
HCC
Xenograft models

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2015.02.036

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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

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title = "Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma",

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.",

keywords = "Antibody therapy, CD47, HCC, Xenograft models",

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

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Ireland Ltd.",

year = "2015",

month = may,

day = "1",

doi = "10.1016/j.canlet.2015.02.036",

language = "English (US)",

volume = "360",

pages = "302--309",

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T1 - Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma

AU - Xiao, Zhenyu

AU - Chung, Haniee

AU - Banan, Babak

AU - Manning, Pamela T.

AU - Ott, Katherine C.

AU - Lin, Shin

AU - Capoccia, Benjamin J.

AU - Subramanian, Vijay

AU - Hiebsch, Ronald R.

AU - Upadhya, Gundumi A.

AU - Mohanakumar, Thalachallour

AU - Frazier, William A.

AU - Lin, Yiing

AU - Chapman, William C.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

KW - Antibody therapy

KW - CD47

KW - HCC

KW - Xenograft models

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DO - 10.1016/j.canlet.2015.02.036

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SN - 0304-3835

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SP - 302

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JO - Cancer Letters

JF - Cancer Letters

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ER -

Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma

Abstract

Keywords

ASJC Scopus subject areas

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