ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Aptamers are short single-stranded oligonucleotides that fold into well defined three-dimensional shapes allowing them to bind to and inhibit their targets with high affinity and specificity. Aptamers can be considered truly multifunctional tools, because they can be generated rapidly and applied for specific detection, inhibition, and characterization of proteins. Recent publications impressively confirm that aptamers can be used either as surrogate inhibitors for the identification of small molecule lead compounds or as biopharmaceuticals.

ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Cancer is a difficult target for any therapeutic strategy; therefore, there is a continuous search for new therapeutic modalities, for application either alone or in combination. In this regard, gene-based therapy is a new approach that offers hope of improved control of tumors. Intensive research to apply gene therapy for cancer treatment has led to identification of the most important technical and theoretical barriers that need to be overcome for clinical success. One of the central unresolved challenges remains the issue of specific and efficient delivery of genes to target cells or tissues, emphasizing the importance of the gene carrier. Along with different viral and non-viral vector systems, mammalian cells have also been considered as vehicles for delivery of anti-cancer therapeutics. The cell-based delivery approach was introduced as the first attempt to apply gene therapy to cancer treatment, and in general, has followed most of the ups and downs of gene therapy applications, progressing alongside new knowledge gained in this field. As a result, significant progress has been made in some aspects of the cell-based approach, while the development of other essential issues is only just gaining speed. It appears that the initial phase of development of cell-based protocols – the achievement of efficientex vivocell loading with therapeutics – has largely been fulfilled. However, the desired efficacy of cell-based strategies in general has not yet been reached, and specificity of tumor homing needs to be improved considerably. There is hope that advances in related scientific fields will promote the utilization of cells as powerful and versatile vehicles for cancer gene therapy.

ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

The development of new cancer immunodiagnostic tests measuring soluble markers can be divided along the lines of single analyte measurement versus multiplex analysis. In the measurement of single analytes, newly proposed test analytes still struggle with the same issues as their predecessors; namely, can the measurement of a single biomarker be sufficiently sensitive and specific for screening the general population? Probably the best example of this challenge is in the area of bladder cancer detection, where several newly identified markers are being clinically evaluated in multicenter trials. In order to surmount this hurdle, multiplex analysis has become an increasingly important research focus. By combining the statistical power of measuring many cancer-associated analytes, it is hoped that highly specific diagnostic tests can be developed that are suitable for screening the general population. Some of the most impressive data for multiplex cancer biomarker detection derive from a non-immunologic technique – mass spectroscopy. Multiplex analysis has also recently been applied to the measurement of serum antibodies to tumor-associated antigens. Recent data link the development of antibodies to tumor-associated antigens with the presence of solid tumors. This strategy is a departure from the more traditional assay format of measuring the antigens themselves, and is another promising emerging area of investigation for the early detection of solid tumors.Solid tumor analysis by quantitative immunohistochemical staining is another rapidly growing area of cancer immunodiagnosis. This field has become especially important in the context of pharmacodiagnostics – the coupling of cancer therapy to the outcome of a test measurement from a patient biopsy. Standardization and assay reproducibility appear to be the most significant challenges in this context. In summary, developments over the past several years give reason for excitement and optimism about the potential for cancer immunodiagnostics to meaningfully impact cancer patient survival. In this review we take a fresh look at the field of cancer immunodiagnostics, to identify these recent and emerging trends that may impact on clinical practice over the next few years.

ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Background and objectives‘Biogenerics’ regulation has brought about a heated debate within the EU as the first biopharmaceuticals are going off patent. This study aims to examine the opportunities and challenges offered by biogenerics by surveying the viewpoints of experts in regulatory agencies and in companies developing novel biopharmaceuticals and biogenerics.MethodsOral interviews were conducted in 2002 and 2003 with experts including representatives of the European Generic Medicines Association (EGA) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) in Brussels, three innovator biotech companies, and five other experts in Finland. Additionally, four biogenerics companies and one innovator company abroad answered a structured, written questionnaire.Results and conclusionAccording to this study, biogenerics should be regulated on a case-by-case basis. The interviewees were not unanimous as to whether comparability can be addressed and which are the most challenging areas for proving comparability. Immunogenicity was considered to be a major problem for biogenerics. Therefore, a requirement for an intensified monitoring of the safety profile during post-marketing was thought to be justified in many cases.

ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

BackgroundInterferon (IFN)-α-2b therapy has been shown to improve clinical conditions of patients with chronic hepatitis C. Several studies showed that the addition of ribavirin to IFNα-2b greatly improved the biochemical as well as the virologic and histological response rate in patients with chronic hepatitis C. The aim of this study was to evaluate biochemical, virologic, and histological responses as well as adherence to a treatment employing ribavirin plus low doses of recombinant interleukin (IL-2) or IFNα-2b in subjects with chronic active hepatitis C, which relapsed or did not respond to previous treatment with interferon alone.Patients and methodsWe evaluated all 75 consecutive adult patients with chronic hepatitis C admitted to our department, who were previously treated with one course of recombinant or lymphoblastoid IFNα-2b (3 million to 6 million IU three times a week for at least 4 months), and either relapsed or did not respond to this treatment. Sixty patients met the inclusion criteria for enrollment in our study. Randomization was performed on the basis of a computer-generated list. The treatment schedule was based on subcutaneous administration of recombinant IFNα-2b (Intron®A) at a dosage of 3 million IU every day, or IL-2 (aldesleukin) at a dose of 1 million IU every day, with oral ribavirin administered 400mg twice daily (morning and night) [for patients weighing <75kg] or 500mg twice daily (for those weighing ≥75kg). The planned treatment period was 6 months.ResultsBoth IFN and IL-2 treatment groups achieved a significant biochemical response with respect to baseline values at the end of the treatment (p < 0.0001 for both) and at the end of the follow up (p < 0.001 for both). The differences between the two groups at the end of treatment and at the end of the follow up were significant (p < 0.04 and p < 0.003 respectively) in favor of IL-2-treatment. The virologic response rate for IL-2-treated patients was significantly higher than for IFN-treated patients at months 3 (p < 0.05) and 6 (p < 0.05) of the treatment. Both groups showed significant improvement in histological activity index with respect to baseline values, but the difference between the groups was not significant. No withdrawals have been registered.ConclusionThe combination of IL-2 and ribavirin seems to increase the probability of a sustained biochemical and virologic response in patients with chronic hepatitis C that is unresponsive to IFN. Our study showed that IL-2 plus ribavirin may provide a clinically important option that appears to be well tolerated and effective in patients with chronic hepatitis C virus infection.

ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Omalizumab (Xolair®) is a humanized monoclonal antibody used in the treatment of adolescent and adult patients with moderate to severe allergic asthma inadequately controlled with inhaled corticosteroids (ICS). It selectively binds to circulating immunoglobulin E (IgE) and, thereby, prevents binding of IgE to mast cells and other effector cells. Without surface-bound IgE, these cells are unable to recognize allergens, thus preventing cellular activation by antigens and the subsequent allergic/asthmatic symptoms. Omalizumab decreases free serum IgE levels in a dose-dependent manner, reduces IgE receptor density on effector cells, and significantly improves airway inflammation parameters.Omalizumab is slowly absorbed after subcutaneous administration, and mean elimination half-life is 26 days, thus allowing infrequent administration of the drug. Omalizumab dosage is determined by bodyweight and pretreatment serum total IgE levels. Patients treated with subcutaneous omalizumab in clinical trials received a dosage that was approximately equal to 0.016 mg/kg/IgE (IU/mL) per 4 weeks. Thus, patients received 150 or 300mg every 4 weeks, or 225, 300, or 375mg every 2 weeks.In adults and adolescents (≥12 years of age) with moderate to severe allergic asthma, subcutaneous administration of omalizumab as add-on therapy with ICS improved the number of asthma exacerbations, rescue medication use, asthma symptom scores, and quality-of-life (QOL) scores compared with placebo during 28- and 32-week double-blind trials. In addition, concomitant ICS use was significantly decreased in patients receiving omalizumab, and in the two largest double-blind trials approximately 40% of omalizumab recipients completely withdrew from ICS therapy while maintaining effective asthma control. In general, results of extension studies showed that the beneficial effects of omalizumab were maintained over a total period of 52 weeks.Omalizumab was well tolerated as add-on therapy with ICS during treatment for up to 52 weeks. Common adverse events in clinical trials included injection site reaction, viral infection, upper respiratory tract infection, sinusitis, headache, and pharyngitis, although the incidence of adverse events with omalizumab was similar to that with placebo.In conclusion, omalizumab, as add-on therapy with ICS, is an effective and well tolerated agent for the treatment of moderate to severe allergic asthma in adolescents and adults. In addition to its symptomatic and QOL benefits, omalizumab therapy allows ICS dosage reduction or discontinuation of ICS in many patients. Comparisons of omalizumab with other asthma therapies have yet to be conducted; however, clinical efficacy and tolerability data indicate that omalizumab is a valuable option in the treatment of allergic asthma.

ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS