RATIONALE: Interferon alfa may interfere with the growth of the cancer cells. It is not yet known if this treatment is more effective than observation following surgery for stage III melanoma.
PURPOSE: Randomized phase III trial to determine the effectiveness of interferon alfa in treating patients who have undergone surgery for stage III melanoma.

Start Date01 Jun 2000

Sponsor / Collaborator

Eortc

100 Clinical Results associated with Pegylated interferon-alpha

100 Translational Medicine associated with Pegylated interferon-alpha

100 Patents (Medical) associated with Pegylated interferon-alpha

834

Literatures (Medical) associated with Pegylated interferon-alpha

01 Jan 2025·Hepatology

Neutralizing antibodies to interferon alfa arising during peginterferon therapy of chronic hepatitis B in children and adults: Results from the HBRN Trials

Article

Author: Feld, Jordan J. ; Janssen, Harry L.A. ; Mosa, Alexander I. ; Chung, Raymond T. ; Salimzadeh, Loghman ; Schwarz, Kathleen B. ; Lin, Hsing-Hua Sylvia ; Gehring, Adam J. ; Perrillo, Robert P. ; Zahoor, Muhammad Atif ; Feld, Joshua B.

Background & Aims:Pegylated interferon-α (PegIFNα) is of limited utility during immunotolerant or immune active phases of chronic hepatitis B infection but is being explored as part of new cure regimens. Low/absent levels of IFNα found in some patients receiving treatment are associated with limited/no virological responses. The study aimed to determine if sera from participants inhibit IFNα activity and/or contain therapy-induced anti-IFNα antibodies.Approach & Results:Pre-treatment, on-treatment, and post-treatment sera from 61 immunotolerant trial participants on PegIFNα/entecavir therapy and 88 immune active trial participants on PegIFNα/tenofovir therapy were screened for anti-IFNα antibodies by indirect ELISA. The neutralization capacity of antibodies was measured by preincubation of sera±recombinant human IFNα added to Huh7 cells with the measurement of interferon-stimulated gene (ISG)-induction by qPCR. Correlations between serum-induced ISG inhibition, presence, and titer of anti-IFNα antibodies and virological responses were evaluated. Preincubation of on-treatment serum from 26 immunotolerant (43%) and 13 immune active (15%) participants with recombinant-human IFNα markedly blunted ISG-induction in Huh7 cells. The degree of ISG inhibition correlated with IFNα antibody titer (p < 0.0001; r = 0.87). On-treatment development of anti-IFNα neutralizing antibodies (nAbs) was associated with reduced quantitative HBsAg and qHBeAg declines (p < 0.05) and inhibited IFNα bioactivity to 240 weeks after PegIFNα cessation. Children developed anti-IFNα nAbs more frequently than adults (p = 0.004) but nAbs in children had less impact on virological responses.Conclusions:The development of anti-IFNα nAbs during PegIFNα treatment diminishes responses to antiviral therapy. Understanding how and why anti-IFNα antibodies develop may allow for the optimization of IFN-based therapy, which is critical given its renewed use in HBV-cure strategies.

01 Jan 2025·Virus Research

Achieving chronic hepatitis B functional cure: Factors and potential mechanisms

Review

Author: Zheng, Jiarui ; Qiu, Zixuan ; Jiang, Suzhen ; Feng, Bo ; Huang, Linxiang ; Wang, Zilong ; Xie, Yandi

Chronic hepatitis B (CHB) is a significant global health issue affecting approximately 254 million individuals worldwide. Achieving the loss of hepatitis B surface antigen (HBsAg), either with or without seroconversion to hepatitis B surface antibody (HBsAb), is regarded as a functional cure and the optimal goal for addressing CHB, and can be achieved through various approaches, including induction with nucleos(t)ide analogues (NAs), induction with pegylated interferon alpha (PegIFNα), and spontaneous clearance of HBsAg. Spontaneous clearance of HBsAg is rare, while NAs can directly inhibit HBV DNA, they are unable to act on covalently closed circular DNA (cccDNA), hence inhibiting HBsAg production or clearing HBsAg is extremely challenging. On the other hand, functional cure based on PegIFNα shows good long-term durability, but over 10 % of patients still experience relapse, mostly within 48 weeks after functional cure. Factors related to CHB functional cure with antiviral therapy are complex, including host factors, viral factors, environmental factors, etc. The integration of HBV DNA into liver cells, persistence of HBV cccDNA, insufficient B cell responses and compromised T cell function pose significant barriers to HBV clearance. Therefore, this study systematically reviewed the relevant factors and potential mechanisms influencing functional cure CHB, which can provide a basis for personalized treatment, help predict treatment outcomes and assess prognosis, and provide theoretical support for the advancement of novel treatment strategies and medications.

01 Dec 2024·Journal of Hepatology

Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B

Article

Author: Zhu, Yue-Yong ; Ou, Qi-Shui ; Li, Jie ; Chen, Jing ; Jiang, Jia-Ji ; Wang, Long-Fei ; Zheng, Qi ; Zeng, Da-Wu ; Zheng, Zi-Zheng ; Zhang, Jian-Wei ; Xue, Han-Xin ; Li, Chen ; Wang, Si-Ling ; Xun, Zhen ; Lai, Rui-Min ; Chen, Tian-Bin

BACKGROUND & AIMSThe changes in HBV-specific B cells in patients with chronic hepatitis B (CHB) undergoing pegylated interferon-α (PEG-IFNα) treatment and achieving functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B cells.METHODSWe included 39 nucleos(t)ide analogue-treated patients with CHB who received sequential combination therapy with PEG-IFNα and eight treatment-naïve patients. HBV-specific B cells were characterized ex vivo using fluorescently labeled hepatitis B surface and core antigens (HBsAg and HBcAg). The frequency, phenotype, and subsets of HBV-specific B cells and follicular helper T cells (Tfh cells) were detected using flow cytometry. The functionality of HBV-specific B cells was quantified through ELISpot assays.RESULTSDuring treatment, the fraction of activated memory B cells (MBCs) among HBsAg-specific B cells and the expression of IgG, CXCR3, and CD38 increased. The antibody-secretion capacity of HBsAg-specific B cells was only restored in patients achieving a functional cure after treatment and it positively correlated with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG⁺ classical MBCs and plasmablasts among HBsAg-specific B cells. HBcAg-specific B cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM⁺ atypical type of MBC after treatment, irrespective of functional cure. The number of CD40L⁺ Tfh cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation.CONCLUSIONSAfter PEG-IFNα treatment, HBsAg- and HBcAg-specific B cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L⁺ Tfh cells is associated with the active recovery of HBsAg-specific B cells.IMPACT AND IMPLICATIONSHBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of patients with chronic hepatitis B offers a promising therapeutic strategy for viral clearance, e.g. via therapeutic vaccination. We analyzed the alterations in HBV-specific B cells in patients treated with pegylated interferon-α and identified novel pathways for immunotherapeutic boosting of B cell immunity.

100 Deals associated with Pegylated interferon-alpha

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Indication	Highest Phase	Country/Location	Organization	Date
Melanoma, Cutaneous Malignant	Phase 2	Australia	Eortc	01 Jun 2000
Melanoma, Cutaneous Malignant	Phase 2	Croatia	Eortc	01 Jun 2000
Melanoma, Cutaneous Malignant	Phase 2	Poland	Eortc	01 Jun 2000
Melanoma, Cutaneous Malignant	Phase 2	Czechia	Eortc	01 Jun 2000
Melanoma, Cutaneous Malignant	Phase 2	Netherlands	Eortc	01 Jun 2000
Melanoma, Cutaneous Malignant	Phase 2	France	Eortc	01 Jun 2000
Melanoma, Cutaneous Malignant	Phase 2	Germany	Eortc	01 Jun 2000
Melanoma, Cutaneous Malignant	Phase 2	Estonia	Eortc	01 Jun 2000
Melanoma, Cutaneous Malignant	Phase 2	Belgium	Eortc	01 Jun 2000
Melanoma, Cutaneous Malignant	Phase 2	Switzerland	Eortc	01 Jun 2000

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