Novel Abs targeting the N-terminus of fibroblast growth factor 19 inhibit hepatocellular carcinoma growth without bile-acid-related side-effects.
Cancer Sci
; 111(5): 1750-1760, 2020 May.
Article
em En
| MEDLINE
| ID: mdl-32061104
ABSTRACT
Hepatocellular carcinoma (HCC) is a common and particularly fatal form of cancer for which very few drugs are effective. The fibroblast growth factor 19 (FGF19) has been viewed as a driver of HCC development and a potential Ab target for developing novel HCC therapy. However, a previously developed anti-FGF19 Ab disrupted FGF19's normal regulatory function and caused severe bile-acid-related side-effects despite of having potent antitumor effects in preclinical models. Here, we developed novel human Abs (G1A8 and HS29) that specifically target the N-terminus of FGF19. Both Abs inhibited FGF19-induced HCC cell proliferation in vitro and significantly suppressed HCC tumor growth in mouse models. Importantly, no bile-acid-related side effects were observed in preclinical cynomolgus monkeys. Fundamentally, our study demonstrates that it is possible to target FGF19 for anti-HCC therapies without adversely affecting its normal bile acid regulatory function, and highlights the exciting promise of G1A8 or HS29 as potential therapy for HCC.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
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Fatores de Crescimento de Fibroblastos
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Neoplasias Hepáticas
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Anticorpos
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cancer Sci
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China