Anti-CD47 antibody suppresses tumour growth and augments the effect of chemotherapy treatment in hepatocellular carcinoma.
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-CD47 antibody alone and in combination with chemotherapy in HCC.



In this study, we examined the functional effects of anti-CD47 antibody (B6H12) 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-CD47 antibody alone or in combination with doxorubicin was examined in patient-derived HCC xenograft.



Blocking CD47 with anti-CD47 monoclonal antibody (B6H12) at 10 μg/ml could suppress self-renewal, tumourigenicity and migration and invasion abilities of MHCC-97L and Huh-7 cells. Interestingly, anti-CD47 antibody synergized the effect of HCC cells to chemotherapeutic drugs including doxorubicin and cisplatin. Blockade of CD47 by anti-CD47 antibody induced macrophage-mediated phagocytosis. Using a patient-derived HCC xenograft mouse model, we found that anti-CD47 antibody (400 μg/mouse) in combination with doxorubicin (2 mg/kg) exerted maximal effects on tumour suppression, as compared with doxorubicin and anti-CD47 antibody alone.



Anti-CD47 antibody treatment could complement chemotherapy which may be a promising therapeutic strategy for the treatment of HCC patients.
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Jessica
J
Lo
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Eunice Yuen Ting
EY
Lau
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Francis Tak Yuk
FT
So
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Ping
P
Lu
Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Vera Sau Fong
VS
Chan
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Vincent Chi Ho
VC
Cheung
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Rachel Hiu Ha
RH
Ching
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Bowie Yik Ling
BY
Cheng
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Mark Kin Fai
MK
Ma
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Irene Oi Lin
IO
Ng
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Terence Kin Wah
TK
Lee
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051928:CD47 Antigen / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D051928:CD47 Antigen; C497894:CD47 protein, human; D004317:Doxorubicin; D002945:Cisplatin
CD47; HCC; chemoresistance