Expert opinion on biological therapy
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Expert Opin Biol Ther · Apr 2003
ReviewTherapy of allergic bronchial asthma with omalizumab - an anti-IgE monoclonal antibody.
The immunoglobulin E (IgE) antibody plays a central role in the allergic immune responses, such as those which characterise allergic bronchial asthma. The ability to reduce circulating IgE by using anti-IgE antibodies represents a novel therapeutic approach for IgE-mediated allergic diseases. Omalizumab (rhuMAb-E25/Xolair Genentech, USA/Tanox, Inc., USA/Novartis Pharma AG, Switzerland) is a non-anaphylactogen humanised murine monoclonal antibody which binds to circulating IgE. ⋯ It reduces the frequency of asthma exacerbations and the need for inhaled corticosteroids (ICSs), and improves asthma symptoms, lung function and quality of life. The anti-IgE approach to asthma treatment has a number of further potential advantages, such as the treatment of other concomitant atopic diseases (allergic conjunctivitis and rhinitis, atopic dermatitis and food allergy), regardless of the type of allergic sensitisation (seasonal or perennial). On the basis of several studies, omalizumab is likely to provide a new strategy for treating atopic asthma.
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Expert Opin Biol Ther · Aug 2002
ReviewCancer-testis antigens: promising targets for antigen directed antineoplastic immunotherapy.
During the last decade, the aberrant expression of normal testicular proteins in neoplastically transformed cells became common knowledge. Cancer-testis antigens (CTAs) represent a novel family of immunogenic proteins. The genes MAGE, BAGE, GAGE, LAGE and NY-ESO-1 code for antigens that are recognised on various neoplastically transformed cells by autologous, cytolytic CD8 ( + ) T lymphocytes. ⋯ The identification of neoplasm-associated markers recognised by cellular or humoral effectors of the immune system has opened new perspectives for antigen directed, individualised antineoplastic immunotherapy. In preparation for this new era of targeted immunotherapy, a number of neoplasm-associated antigen families have been identified as targets for CD8+, cytolytic T lymphocytes in vitro and in vivo : (1) CTAs expressed in various neoplasms and in normal testis, restricted to male germ cells; (2) melanocyte differentiation antigens; (3) point mutations of normal genes; (4) antigens overexpressed in neoplastic tissues; and (5) viral antigens. Immunotherapeutic protocols directed against the CTAs have already been initiated to analyse the induction of antigen-specific cellular and humoral immune responses in vivo.
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Expert Opin Biol Ther · Aug 2002
ReviewDrotrecogin alfa: a new approach in the treatment of severe sepsis.
Severe sepsis is a common and frequently fatal condition. Evidence showing a link between the coagulation system and the inflammatory response to sepsis led to the development of drotrecogin alfa (activated) as an agent in the treatment of sepsis. ⋯ Although associated with an increased risk of bleeding, this is usually procedure-related rather than spontaneous. Although costly, this is a drug that effectively reduces mortality rates in patients with severe sepsis.
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Concerns about the infectious and immunosuppressive risks of allogeneic blood products persist, and the increased disproportion of blood donation and consumption has reinforced the search for alternative erythrocyte transfusion strategies in recent years. With the absence of problems such as nephro-toxicity, increased colloid osmotic pressure and sudden renal clearance, modern haemoglobin based oxygen carriers (HBOC) have shown their effectiveness and tolerability in numerous animal and several clinical studies. HBOC can be infused without prior cross-matching and are now available as stable formulations with long shelf-life. ⋯ In addition to significant plasmatic oxygen transport, HBOC also enhance tissue oxygenation because of the facilitated oxygen release by HBOC and from remaining erythrocytes. Further studies will show, if the outcome of patients with impaired perfusion (e.g., stroke or myocardial infarction) can be improved by prophylactic or therapeutic application of HBOC. Whenever these formulations are globally launched, they will find differential indications as potent oxygen-delivering drugs in addition to the globally recognised goal of red cell substitutes in cases of bleeding.
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Expert Opin Biol Ther · Jul 2001
ReviewPapillomavirus-like particle based vaccines: cervical cancer and beyond.
Non-infectious human papillomavirus-like particles (VLP), composed of the L1 major capsid protein, are under active development as vaccines to prevent cervical cancer. They would presumably function primarily by generating virion-neutralising antibodies against the genital human papillomavirus (HPV) types that are the principal cause of most cervical cancers. Early phase clinical studies indicate that the VLP vaccines are well tolerated and able to consistently induce high titres of virus type-specific neutralising antibodies. ⋯ The display of self polypeptides in the context of the highly ordered array of repetitive elements on the papillomavirus VLP surface abrogates the ability of the humoral immune system to functionally distinguish between foreign and self. High titre and high avidity auto-reactive IgG antibodies have been induced to both soluble (TNF-alpha) and cell surface (CCR5) central self-antigens. Vaccines based on this approach could potentially be effective alternatives to monoclonal antibody (mAb)-based therapies for a variety of disease targets.