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Anti-IL-20 monoclonal antibody inhibited tumor growth in hepatocellular carcinoma.

ABSTRACT: Interleukin (IL)-20 is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and osteoporosis. However, the role of IL-20 in hepatocellular carcinoma (HCC) is unclear. We explored the function of IL-20 in HCC. Tumor tissue samples were analyzed the expression of IL-20 and cyclin D1 by using immunohistochemistry staining and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. To examine the role of anti-IL-20 monoclonal antibody (7E) in tumor growth, BALB/c mice was injected with ML-1 cells and treated with 7E. HCC tumor tissue expressed higher levels of IL-20 than did non-tumor tissue. High IL-20 expression in HCC was correlated with poor overall survival (relative risk:>3). IL-20 and cyclin D1 expression were also highly correlated in HCC patient specimens and 3 human HCC cell lines. IL-20 also increased cell proliferation and migration, and it regulated matrix metalloproteinase (MMP)-13, tumor necrosis factor (TNF)-?, cyclin D1, and p21WAF1 expression in ML-1 cells. 7E attenuated tumor growth in mice inoculated with ML-1 cells. The expression of cyclin D1, TNF-?, MMP-9, and vascular endothelial growth factor was significantly inhibited after 7E treatment. The findings of this study suggest that IL-20 plays a role in the tumor progression of HCC.

SUBMITTER: Chiu YS

PROVIDER: S-EPMC5730582 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Anti-IL-20 monoclonal antibody inhibited tumor growth in hepatocellular carcinoma.

Chiu Yi-Shu YS Hsing Chung-Hsi CH Li Chien-Feng CF Lee Chon-Yee CY Hsu Yu-Hsiang YH Chang Ming-Shi MS

Scientific reports 20171214 1

Interleukin (IL)-20 is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and osteoporosis. However, the role of IL-20 in hepatocellular carcinoma (HCC) is unclear. We explored the function of IL-20 in HCC. Tumor tissue samples were analyzed the expression of IL-20 and cyclin D1 by using immunohistochemistry staining and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. To examine the role of anti-IL-20 monoclonal antibody (7E) in tumor growth, BALB/ ...[more]

PMID: 29242565

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Project description:BackgroundThe current trial was a first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the recombinant monoclonal anti-interleukin-20 (IL-20) antibody, NNC0109-0012, which targets the inflammatory cytokine IL-20.MethodsIn total, 48 patients aged 18 to 75 years with moderate to severe stable chronic plaque psoriasis with affected body surface area ≥15% and physician global assessment score ≥3 were enrolled in this randomized, double-blind, multicenter, placebo-controlled, phase 1 dose-escalation trial. Patients were randomized within each single dose cohort (0.01, 0.05, 0.2, 0.6, 1.5, or 3.0 mg/kg) or multiple dose cohort (0.05, 0.2, 0.5, 1.0, or 2.0 mg/kg; 1 dose every other week for 7 weeks) of NNC0109-0012 or placebo in a 3:1 ratio. In the expansion phase, 7 patients were randomized to weekly doses of 2.0 mg/kg NNC0109-0012 or placebo for 7 weeks. The primary objective, safety and tolerability, was assessed by evaluating adverse events (AEs). Additional endpoints included pharmacokinetics, pharmacodynamics, and clinical response (assessed using the Psoriasis Area and Severity Index [PASI] score).ResultsAEs were reported in 85% of patients (n = 40) in the initial study phases (NNC0109-0012, 83%; placebo, 92%) and in 4 of 7 patients in the multiple-dose expansion phase. One serious AE was reported but was judged not to be causally related to NNC0109-0012. No dose-limiting toxicities were reported. NNC0109-0012 pharmacokinetics was similar to other monoclonal antibodies, with an average half-life of approximately 3 weeks. There was a dose-proportional increase in area under the curve and maximum concentration after single dosing. No substantial changes in pharmacodynamic parameters were observed. The expansion phase was terminated early due to apparent lack of PASI improvement.ConclusionSingle and multiple doses of NNC0109-0012, ranging from 0.05 to 3.0 mg/kg, were well tolerated in patients with psoriasis and exhibited pharmacokinetics similar to that of other monoclonal antibodies.Trial registrationClinicalTrials.gov NCT01261767.

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Anti-IL-20 monoclonal antibody inhibited tumor growth in hepatocellular carcinoma.

Publications

Anti-IL-20 monoclonal antibody inhibited tumor growth in hepatocellular carcinoma.

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