Interferon Alfa-2b Research Articles

Role of Tumor Necrosis Factor alpha promoter polymorphisms in interferon related side effects in chronic hepatitis B patients under interferon alpha 2b treatment

Objective(s). Interferon alpha therapy is associated with series of adverse effects leading premature discontinuation of treatment. Here we aimed to determine the effects of Tumor necrosis alpha promoter polymorphisms on interferon related side effects during interferon alpha 2b treatment in chronic hepatitis B patients
 Material and Method(s). This observational study enrolled 50 chronic hepatitis B patients, who were treated with interferon alpha 2b 10 tiw plus lamivudine 100mg/day at Selçuk University Meram Medical Faculty Department of Infectious Diseases and Clinical Bacteriology between 2006-2007. Patients were followed-up with complete blood count, transaminases and amylase monthly at out patient clinics of our department. All patients were asked to fill a questionnaire to evaluate the interferon related side effects at every visit. Tumor necrosis factor alpha -238 and -308 polymorphisms were investigated with PCR-Restriction fragment length polymorphisms.
 Result(s) and Conclusion Arthralgia was present in 93.8% of patients. Exhaustion, loss of appetite, mount dryness and fever are the leading complaints of the patients. Median complaint scores were 9, 9.5, 11 and 5 at 4th, 12th, 24th and 48th week visits, respectively. Thrombocytopenia and leucopenia were detected in 8 (16%) and 5 (10%) patients, respectively. One-third of the patients reported depressive mood however, depression was diagnosed in 5 (10%) patients. TNF alpha promoter 238GG and 308GG allele was present in 42/50 and 43/50 patients, respectively. No association was found between TNF promoter allele and certain patient-reported side effect, complaint score, hematological and psychological adverse effects. TNF alpha promoter polymorphisms do not contribute to occurrence of IFN alpha treatment related side effects.

Absence of mutations in the human interferon alpha-2b gene in workers chronically exposed to ionising radiation.

Individuals chronically exposed to low-level ionising radiation (IR) run the risk of harmful and long-term adverse health effects, including gene mutations and cancer development. The search for reliable biomarkers of IR exposure in human population is still of great interest, as they may have a great implementation potential for the surveillance of occupationally exposed individuals. In this context, and considering previous literature, this study aimed to identify mutations in the human interferon alpha-2b (hIFNα-2b) as a potential biomarker of occupational chronic low-dose IR exposure linking low-IR exposure to the effects on haematopoiesis and reduced immunity. The analysis was performed in the genomic DNA of 51 uranium miners and 38 controls from Kazakhstan, and in 21 medical radiology workers and 21 controls from Italy. hIFNα-2b gene mutations were analysed with the real-time polymerase chain reaction (PCR) or Sanger sequencing. However, none of the investigated workers had the hIFNα-2b mutation. This finding highlights the need for further research to identify biomarkers for early detection of health effects associated with chronic low-dose IR exposure.

Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach

Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities. The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects. Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost. Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property. Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs. Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans. Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS). The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively. Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.

Sustained serological and complete responses in HBeAg-positive patients treated with Peginterferon alfa-2b: a 6-year long-term follow-up of a multicenter, randomized, controlled trial in China

BackgroundPegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial.MethodsEligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 μg/kg/wk. 24 weeks or 1.5 μg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA < 2000 IU/mL.ResultsThe proportions of patients achieving sustained SR among patients who had SR at EOS were high in three treatment groups (61.9, 65.5, 76.5%, respectively, p = 0.46); treatment with PEG-IFN alfa-2b 1.5 μg/kg/wk. 48 weeks had the highest proportion of a sustained CR among patients who had CR at EOS (75.0%, p = 0.05). A considerable number of patients achieved sustained SR (18.2–29.9%) and sustained CR (14.8–18.3%) after EOS despite no further NA treatment. At the LTFU, rates of SR and CR were less than 70.0 and 50.0%, respectively, among all enrolled patients regardless of additional nucleos(t)ide analogs before the LTFU.ConclusionsPEG IFN alfa-2b therapy had considerable off-treatment sustainability in Chinese HBeAg positive chronic hepatitis B patients with serological and complete responses.

Aspirin and Rintatolimod With or Without Interferon-alpha 2b in Treating Patients With Prostate Cancer Before Surgery

Aspirin and Rintatolimod With or Without Interferon-alpha 2b in Treating Patients With Prostate Cancer Before Surgery

High level extracellular production of recombinant human interferon alpha 2b in glycoengineered Pichia pastoris: culture medium optimization, high cell density cultivation and biological characterization.

The present study was aimed at design of experiments (DoE)- and artificial intelligence-based culture medium optimization for high level extracellular production of a novel recombinant human interferon alpha 2b (huIFNα2b) in glycoengineered Pichia pastoris and its characterization. The artificial neural network-genetic algorithm model exhibited improved huIFNα2b production and better predictability compared to response surface methodology. The optimized medium exhibited a fivefold increase in huIFNα2b titre compared to the complex medium. A maximum titre of huIFNα2b (436mgl-1 ) was achieved using the optimized medium in the bioreactor. Real-time capacitance data from dielectric spectroscopy were utilized to model the growth kinetics with unstructured models. Biological characterization by antiproliferative assay proved that the purified recombinant huIFNα2b was biologically active, exhibiting growth inhibition on breast cancer cell line. Culture medium optimization resulted in enhanced production of huIFNα2b in glycoengineered P. pastoris at both shake flask and bioreactor level. The purified huIFNα2b was found to be N-glycosylated and biologically active. DoE-based medium optimization strategy significantly improved huIFNα2b production. The antiproliferative activity of huIFNα2b substantiates its potential scope for application in cancer therapy.

Current Status and Future Directions of Immunotherapy in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) was recognized as an immunologically sensitive cancer over 30years ago. The first therapies to affect the course of RCC were cytokines (interferon alfa-2B and interleukin-2). Subsequently, drugs that inhibit HIF (hypoxia-inducible factor)/VEGF (vascular endothelial growth factor) signaling demonstrated overall survival advantages (tyrosine kinase inhibitors and mTor inhibitors). In the last 3years, the immune checkpoint inhibitors (ICIs) have become the standard of care treatments in the first and second lines for RCC. Emerging data show that combinations of ICI, HIF signaling inhibitors, and cytokines are potentially powerful regimens. How to combine and sequence these types of therapies and how to integrate new approaches into the management of RCC are now the key questions for the field. Treatment of RCC is likely to change dramatically in the next few years.

New opportunities for the combined therapy of allergic rhinitis in real clinical practice

This paper assesses the efficacy of the original combined medication Allergoferon® beta (betamethasone + interferon alpha-2b) in real clinical practice among patients with seasonal allergic rhinitis (AR). The research program results demonstrated a good efficacy of the given medication: there were a decrease in nasal congestion as well as restoration of nasal breathing and in patients with concomitant allergic conjunctivitis - a reduction in the severity of eye symptoms. A low incidence of side effects was observed. It was shown that Allergoferon® beta can be recommended as monotherapy for patients with mild and moderate AR and in complex therapy for patients with severe AR.

Therapeutic effect of combined use of interferon alpha-1b, interleukin-2 and thalidomide on reversing minimal residual disease in acute myeloid leukemia

目的探讨干扰素α-1b、白细胞介素2联合沙利度胺（“干白沙”方案）对急性髓系白血病（AML）患者微小残留病（MRD）的影响。方法对2016年7月至2018年6月收治的18例（17例来自郑州大学附属肿瘤医院，1例来自平顶山市第一人民医院）处于血液学完全缓解但MRD阳性的AML患者应用不同剂量的“干白沙”方案，监测其MRD水平变化。结果18例患者接受常规剂量“干白沙”方案1~2个月，7例患者MRD转阴，3例患者MRD水平明显下降，3例MRD水平升高，5例复发。MRD水平升高的3例患者接受加量的“干白沙”方案，2例MRD转阴，1例MRD水平下降。“干白沙”方案干预治疗MRD阳性AML总有效率为72.2%。根据治疗前MRD水平分组，MRD≥1.0%的患者有效率为57.1%（4/7），MRD<1.0%的患者有效率为81.8%（9/11）。结论“干白沙”方案可使血液学完全缓解但MRD阳性的AML患者MRD转阴或下降，增加方案药物剂量后疗效增加，疗效与治疗前MRD水平可能呈负相关。

Combinations of two drugs among NS3/4A inhibitors, NS5B inhibitors and non-selective antiviral agents are effective for hepatitis C virus with NS5A-P32 deletion in humanized-liver mice.

The emergence of a deletion mutant at hepatitis C virus (HCV) NS5A-P32 (P32del) has recently been reported in a subset of chronic hepatitis C patients who experience virologic failure after direct-acting antiviral drug (DAA) treatment. This mutation confers extremely high resistance to NS5A inhibitors. No effective treatment has been established for cases with this mutation. We used a JFH1-based recombinant virus with NS5A from a genotype 1b strain to introduce a P32del mutation. We inoculated human hepatocyte chimeric mice with sera from a patient with ledipasvir/sofosbuvir therapy failure carrying a genotype 1b HCV with NS5A L31M and P32del or from a DAA-naïve patient carrying wild-type virus. JFH1-based chimeric viruses with P32del showed sufficient levels of replication for in vitro assay despite the suppression of viral growth and infectious virus production. Variants with P32del exhibited severe resistance to all tested NS5A inhibitors, including daclatasvir, ledipasvir, elbasvir and velpatasvir, but were as susceptible to NS3/4A inhibitors, NS5B inhibitors, interferon alfa-2b, and ribavirin as wild-type viruses in the in vitro assay. The P32del mutant virus caused persistent infection in all inoculated chimeric mice with high viral titer and frequency. The virus was resistant to the ledipasvir/GS-558093 (a nucleotide analog inhibitor of NS5B polymerase) regimen but susceptible to either simeprevir plus GS-558093 or peg-interferon alfa-2b, compared to the wild-type virus. Therapies combining at least two drugs among NS3/4A inhibitors, NS5B inhibitors and non-selective antiviral agents may be effective for HCV-infected patients with NS5A-P32del.

West Nile virus encephalitis in GATA2 deficiency

We report a male with longstanding warts who presented with severe West Nile virus encephalitis (WNVE) and recovered after interferon alfa-2b and intravenous immunoglobulin. He was later found to have GATA2 deficiency and underwent successful hematopoietic stem cell transplant.

Drug-induced hyperglycemia in the Japanese Adverse Drug Event Report database: association of evelolimus use with diabetes.

Some categories of drugs are known for causing hyperglycemia or diabetes such as steroids, antipsychotics, and immunosuppressant. However, there has been little evidence from studies about the proportion of each drug in the context of drug-induced diabetes. In this study, we used data from the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system database maintained at the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan, reported between April 2004 and June 2017. Among 459,250 reports of adverse drug reactions in JADER database, reported instances of the adverse event of hyperglycemia or diabetes were extracted. After the exclusion of anti-diabetes drugs, the drugs frequently implicated in the development of hyperglycemia or diabetes, including prednisolone, tacrolimus, everolimus, ribavirin, quetiapine, aripiprazole, interferon alfa-2b, risperidone, atorvastatin, dexamethasone, ciclosporin, nilotinib, methylprednisolone, or nivolumab, were identified. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, was manifested as the third most frequently associated drug with hyperglycemia or diabetes (340 cases), following prednisolone (694 cases) and tacrolimus (393 cases), and the reporting odds ratio (ROR 8.56, 95% CI 7.65-9.57) of this drug was higher than that of the two aforementioned drugs (ROR 3.96, 95% CI 3.66-4.28 and ROR 3.51, 95% CI 3.17-3.89). These results suggest that there is a potent association of evelolimus with hyperglycemia in clinical practice in Japan.

Cloning and Expression of an Optimized Interferon Alpha 2b in Escherichia coli strain BL21 (DE3)

Cloning and Expression of an Optimized Interferon Alpha 2b in Escherichia coli strain BL21 (DE3)

Уменьшение количества вирусэкспрессирующих клеток в плаценте после лечения рекомбинантным интерфероном альфа 2в хронической микст-вирусной инфекции у беременных женщин

Уменьшение количества вирусэкспрессирующих клеток в плаценте после лечения рекомбинантным интерфероном альфа 2в хронической микст-вирусной инфекции у беременных женщин

Usefulness of Topical Interferon Alpha-2b Eye Drop as an Adjunctive Therapy Following Surgical Resection in Ocular Surface Squamous Neoplasia.

To report the clinical course of patients with ocular surface squamous neoplasia treated with topical interferon α-2b (IFNα-2b) after local excision of the tumor. This study enrolled four consecutive Japanese patients comprising one eye with conjunctival carcinoma in situ, and three eyes with squamous cell carcinoma (SCC) diagnosed histopathologically. All of them initially visited Hokkaido University Hospital in 2016. After resecting the tumor tissues, topical IFNα-2b eye drops were given to the eye four times a day. This study retrospectively analyzed the ophthalmological and imaging findings before and after the surgery, based on the patients' medical records. The mean follow-up duration was 37.8 months. All cases were males, and the mean age was 62.3 years. The tumor was located in the bulbar conjunctiva in three cases. Local pedunculated rotation flap, and free conjunctival flap were performed in one and two patients, respectively. In one case with SCC, the tumor involved the lower palpebral conjunctiva, already invading into the orbit at the first visit. The patient underwent extended resection of the lower lid, and reconstruction of the posterior lobe of the eyelid with Hughes flap. Cataract surgery was successfully conducted 18 months after tumor resection. All patients remain well without local recurrence or distant metastasis. Topical IFNα-2b treatment contributed to suppression of tumor recurrence and improvement of quality of vision in patients after local resection of ocular surface squamous neoplasia.

Эффективность применения препарата интерферона альфа-2b для профилактики острых респираторных вирусных инфекций и подготовки к ежегодной туберкулинодиагностике у часто болеющих детей

Эффективность применения препарата интерферона альфа-2b для профилактики острых респираторных вирусных инфекций и подготовки к ежегодной туберкулинодиагностике у часто болеющих детей

Management of Ocular Surface Squamous Neoplasia with Topical and Intralesional Interferon Alpha 2B in Mexicans.

Ocular surface squamous neoplasia (OSSN) is the most common nonpigmented ocular surface neoplasm and it can originate from the conjunctiva and/ or corneal epithelium. Since the rate of recurrence after surgical excision is high, chemotherapeutic and immunotherapeutic agents such as interferon alpha-2b (IFN α-2b) have been used for its treatment. Our objective is to describe the demographic variables of patients with OSSN treated with IFN α-2b and to describe the outcomes of its use in Mexican patients, treated between 2011 and 2017 at Instituto de Oftalmología Fundación Conde de Valenciana. This is a non-randomized retrospective interventional case series. We reviewed the files of patients older than 18 years, with clinical and/or histopathological diagnosis of OSSN, treated with IFN α-2b alone or in combination with surgery, with a minimum of 6 months follow-up. We studied demographic variables, such as gender, age, eye affected and associated risks factors; we also studied the type of therapy with interferon (topical, intralesional and/or associated with surgery), time of treatment, time of follow up, recurrences and complications. A total of 39 patients were included. The mean age of diagnosis was 61 ± 16 years and OSSN was more frequent in males (64.1% of cases). Most of the cases (43.6%) had no identifiable risk factors. The mean time of IFN α-2b treatment was 5 ± 2 months, being higher in the intralesional group (6.5 months) than in the topical group (4.2 months). The clinical resolution with the use of IFN α-2b was evidenced between 0.5 and 10 months, being achieved in 87.1% of the patients. The use of IFN α-2b is effective for the treatment of OSSN with a high success rate (87.1%) and a low incidence of relapse (5 cases), with no reported complications during follow up.

Perspectives dans la maladie de Gorham–Stout

The Gorham–Stout disease belongs to lymphatic abnormalities and corresponds to a lymphatic endothelial cell proliferation under the stimulation of growth factors. This proliferation leads to a bone invasion and progressively to a typical vanishing bone aspect. Fracture risk and its consequences, chylothorax with sometimes fatal issue are the main complications of this disease. Physiopathological mechanisms remain poorly understood. Treatments of this rare bone disease, susceptible to affect every age from infant to adults, rely on bisphosphonates, radiotherapy, surgery, interferon alpha 2b and anti-angiogenic drugs such as sunitinib.

Kidney Cancer Research Network of Canada (KCRNC) consensus statement on the role of cytoreductive nephrectomy for patients with metastatic renal cell carcinoma.

In recent decades, there have been significant advances in the systemic treatment options for patients with metastatic renal cell carcinoma (mRCC) with the introduction of targeted therapies and, more recently, immune checkpoint inhibition. Prior to the introduction of these contemporary therapies for mRCC, two randomized controlled trials identified a survival advantage to performing cytoreductive nephrectomy (CN) followed by interferon alpha-2b vs. interferon alpha-2b alone.1,2 However, whether CN, defined as nephrectomy in the setting of metastatic disease, provides a similar survival advantage for patients receiving modern systemic therapy has remained controversial, with two recent randomized trials calling into question the value of CN.3,4 In addition, several important questions remain surrounding the appropriate application of CN, particularly with regards to optimal patient selection and the timing of surgery. Herein, the Kidney Cancer Research Network of Canada (KCRNC) provides consensus recommendations on the role of CN in patients with mRCC in order to guide clinicians who manage patients with advanced RCC.

Episcleritis in a patient with mucosal melanoma treated with interferon alfa-2b and radiotherapy: a case report

BackgroundMucosal melanoma of the head and neck is a rare malignant tumor associated with a poor prognosis. Surgery, chemotherapy, radiotherapy, and biotherapy are common strategies for treating mucosal melanoma of the head and neck. Episcleritis is an idiopathic, immune-mediated disease, and is classified into two types: simple episcleritis and nodular episcleritis.Case presentationIn this case report we describe ocular changes involving simple episcleritis in a 65-year-old Chinese man with mucosal melanoma of the head and neck after treatment with interferon alfa-2b and radiotherapy. On the third day of interferon alfa-2b treatment, he began to develop simple episcleritis in his left eye. Moreover, the percentage of CD3+ T cells in lymphocytes from blood was increased after interferon alfa-2b treatment. After approximately 6 days, the symptoms of eye pain, hyperemia, and edema disappeared gradually. Then, after radiotherapy was performed three times, he again developed episcleritis in his left eye. The same symptoms of hyperemia and edema occurred again; CD3+ T cell frequency was also at a higher level. After approximately a week, all the symptoms disappeared completely. Simple treatment involving topical ofloxacin and phenylephrine was administered during the two periods of episcleritis.ConclusionEpiscleritis in this patient might have been due to the treatment with interferon alfa-2b and radiotherapy, leading to an increase in the level of CD3+ T cells and activation of immune system cells, which provides the guide for clinical clinicians.