6KTR

Crystal structure of fibroblast growth factor 19 in complex with Fab

Summary for 6KTR

• Entry DOI: 10.2210/pdb6ktr/pdb
• Descriptor: G1A8-Fab-HC, G1A8-Fab-LC, Fibroblast growth factor 19, ... (6 entities in total)
• Functional Keywords: complex, growth factor, antibody, cell cycle, immune system-protein binding complex, immune system/protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 145328.46

Authors

Liu, H.,Zheng, S.,Hou, X.,Liu, X.,Lv, X.,Li, Y.,Li, W.,Sui, J. (deposition date: 2019-08-28, release date: 2020-07-08, Last modification date: 2024-10-23)

Primary citation

Liu, H.,Zheng, S.,Hou, X.,Liu, X.,Du, K.,Lv, X.,Li, Y.,Yang, F.,Li, W.,Sui, J.
Novel Abs targeting the N-terminus of fibroblast growth factor 19 inhibit hepatocellular carcinoma growth without bile-acid-related side-effects.
Cancer Sci., 111:1750-1760, 2020

PubMed 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.

PubMed: 32061104
DOI: 10.1111/cas.14353

Experimental method

X-RAY DIFFRACTION (2.59775753879 Å)