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Anti‐ CD 47 antibody suppresses tumour growth and augments the effect of chemotherapy treatment in hepatocellular carcinoma
Author(s) -
Lo Jessica,
Lau Eunice Yuen Ting,
So Francis Tak Yuk,
Lu Ping,
Chan Vera Sau Fong,
Cheung Vincent Chi Ho,
Ching Rachel Hiu Ha,
Cheng Bowie Yik Ling,
Ma Mark Kin Fai,
Ng Irene Oi Lin,
Lee Terence Kin Wah
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12963
Subject(s) - cd47 , doxorubicin , antibody , cancer research , medicine , monoclonal antibody , in vivo , hepatocellular carcinoma , chemotherapy , cisplatin , in vitro , phagocytosis , immunology , pharmacology , chemistry , biology , biochemistry , microbiology and biotechnology
Background & Aims Hepatocellular carcinoma ( HCC ) is often associated with metastasis and recurrence leading to a poor prognosis. Therefore, development of novel treatment regimens is urgently needed to improve the survival of HCC patients. In this study, we aimed to investigate the in vitro and in vivo effects of anti‐ CD 47 antibody alone and in combination with chemotherapy in HCC . Methods In this study, we examined the functional effects of anti‐ CD 47 antibody ( B 6 H 12) on cell proliferation, sphere formation, migration and invasion, chemosensitivity, macrophage‐mediated phagocytosis and tumourigenicity both in vitro and in vivo . The therapeutic efficacy of anti‐ CD 47 antibody alone or in combination with doxorubicin was examined in patient‐derived HCC xenograft. Results Blocking CD 47 with anti‐ CD 47 monoclonal antibody ( B 6 H 12) at 10 μg/ml could suppress self‐renewal, tumourigenicity and migration and invasion abilities of MHCC ‐97 L and H uh‐7 cells. Interestingly, anti‐ CD 47 antibody synergized the effect of HCC cells to chemotherapeutic drugs including doxorubicin and cisplatin. Blockade of CD 47 by anti‐ CD 47 antibody induced macrophage‐mediated phagocytosis. Using a patient‐derived HCC xenograft mouse model, we found that anti‐ CD 47 antibody (400 μg/mouse) in combination with doxorubicin (2 mg/kg) exerted maximal effects on tumour suppression, as compared with doxorubicin and anti‐ CD 47 antibody alone. Conclusions Anti‐ CD 47 antibody treatment could complement chemotherapy which may be a promising therapeutic strategy for the treatment of HCC patients.