摘要:

Biotechnology companies face ethical challenges of two distinct types: bioethical challenges faced on account of the nature of work in the life sciences, and corporate ethical challenges on account of their nature as commercial entities. The latter set of challenges has received almost no attention at all in the academic literature or media. This paper begins to remedy that lacuna, examining ethical issues that arise specifically on account of the status of biotech companies as commercial entities. The focus here is on three representative issues: product safety, corporate social responsibility, and corporate governance. It is argued that each of these issues poses particular ethical challenges for companies in the biotech sector. In the area of product safety, it is noted that biotech companies face particular challenges in determining what counts as a ‘safe’ product, given the contentious nature of what might count as a ‘harm’ in the biotech field. In the area of corporate social responsibility, the adoption of a ‘stakeholder approach’ and an attempt to manage the social consequences of products pose special challenges for biotech companies. This is due to the enormous range of groups and individuals claiming to have a stake in the doings of such companies, and the trenchant controversies over just what the social consequences of various biotechnologies might be. In the area of corporate governance, biotech companies need to seek out and follow best practices regarding the ways in which information, authority, and influence flow between a company’s shareholders, managers, and Board of Directors, if they are to avoid duplicating the ethical and financial scandal that brought down ImClone. An important meta-issue, here – one that renders each of these corporate ethical challenges more vexing – is the difficulty of finding the appropriate benchmarks for ethical corporate behavior in a field as controversial, and as rapidly evolving, as biotechnology. Three programmatic suggestions can be made: Firstly, scholars and others interested in the ethical performance of the biotech sector must seek out and build opportunities for richer interdisciplinary collaboration. Secondly, companies within the biotech sector must seek out expertise and build capacity and competency in dealing with the corporate ethical issues that arise in their sector. Finally, companies in the biotech sector should explore the opportunities for collective problem solving afforded by the existence of local, national, and international industry associations such as the Biotechnology Industry Organization, BIOTECanada, and EuropaBio.

ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Developing efficient adjuvants for human vaccines that elicit broad and sustained immune responses at systemic or mucosal levels remains a formidable challenge for the vaccine industry. Conventional approaches in the past have been largely empirical and – at best – partially successful. Importantly, recent advances in our understanding of the immune system, most particularly with respect to early proinflammatory signals, are leading to the identification of new biological targets for vaccine adjuvants. This review covers both the current status of adjuvant testing in humans, the residual needs for vaccines in development, and the emerging immunological foundations for adjuvant design. A better understanding of the biology of toll-like receptors, non-conventional T cell subpopulations, T and B cell memory, regulatory T cells, and mucosal immunity has profound implications for a modern approach to adjuvant screening and development. The future lies in the high throughput screening of synthetic chemical entities targeting well-characterized biological molecules. Used alone or in combination, such synthetic adjuvants will allow stimulation or modulation in a safe and efficient manner of strong effector, regulatory and memory immune mechanisms.

ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

The autoimmune response is executed via cognate interactions between effector immune cells and antigen presenting cells. Cognate interactions provide the immune effectors with specific signals generated through the antigen receptor as well as with second, non-specific signals, generated from the interaction of pairs of cell-surface molecules (costimulatory molecules) present on their plasma membrane. Disruption of this second, non-specific costimulatory signal results in the interruption of the productive (auto)immune response, leading to anergy, a state of immune unresponsiveness. The CD28:B7 families of molecules and the CD40:CD40L pair of molecules are considered as critical costimulatory elements. Disruption of the CD28:B7 interaction using a genetically engineered soluble form of the inhibitory molecule CTLA4in vitro, as well as in experimental models of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), led to the inhibition of the autoimmune response. Similarly, promising data stem from the use of an anti-CD40L monoclonal antibody (mAb) in murine SLE.While such treatments prevent the development of autoimmunity in animal models, this preventive approach is inapplicable to human diseases. However, the rational bench-to-bedside approach led investigators to clinical trials of CTLA4-Ig and of two different humanized anti-human CD40L mAbs in patients with RA and SLE, respectively. Initial experience with the use of CTLA4-Ig in patients with RA is encouraging, since in one short-term trial the construct was well-tolerated and produced clinically meaningful improvement of the disease in a significant proportion of those treated. Surprisingly, the anti-CD40L mAb treatment approach in human lupus was not fruitful, since short-term administration of the anti-CD40L mAb ruplizumab in lupus nephritis was correlated with life-threatening prothrombotic activity despite initial encouraging data in the serology and renal function of the patients. Also, IDEC-131 anti-CD40L mAb treatment did not prove to be clinically effective in human SLE, despite being well tolerated. Precise tailoring of the administration schemes for these novel therapeutic modalities is awaited.Finally, conceptually different approaches to block costimulation by inhibiting the induced expression of costimulatory molecules or the transmission of their specific intracytoplasmic signal have already produced encouraging preliminary results.

ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Collagen is the main structural protein in vertebrates. It plays an essential role in providing a scaffold for cellular support and thereby affecting cell attachment, migration, proliferation, differentiation, and survival. As such, it also plays an important role in numerous approaches to the engineering of human tissues for medical applications related to tissue, bone, and skin repair and reconstruction. Currently, the collagen used in tissue engineering applications is derived from animal tissues, creating concerns related to the quality, purity, and predictability of its performance. It also carries the risk of transmission of infectious agents and precipitating immunological reactions. The recent development of recombinant sources of human collagen provides a reliable, predictable and chemically defined source of purified human collagens that is free of animal components. The triple-helical collagens made by recombinant technology have the same amino acid sequence as human tissue-derived collagen. Furthermore, by achieving the equivalent extent of proline hydroxylation via coexpression of genes encoding prolyl hydroxylase with the collagen genes, one can produce collagens with a similar degree of stability as naturally occurring material. The recombinant production process of collagen involves the generation of single triple-helical molecules that are then used to construct more complex three-dimensional structures. If one loosely defines tissue engineering as the use of a biocompatible scaffold combined with a biologically active agent (be it a gene or gene construct, growth factor or other biologically active agent) to induce tissue regeneration, then the production of recombinant human collagen enables the engineering of human tissue based on a human matrix or scaffold. Recombinant human collagens are an efficient scaffold for bone repair when combined with a recombinant bone morphogenetic protein in a porous, sponge-like format, and when presented as a membrane, sponge or gel can serve as a basis for the engineering of skin, cartilage and periodontal ligament, depending on the specific requirements of the chosen application.

ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Adalimumab (Humira®) is a recombinant, fully human IgG1 monoclonal antibody that binds specifically to tumor necrosis factor (TNF)-α, thereby neutralizing the activity of the cytokine. Subcutaneous adalimumab has been investigated in well designed trials in patients with active rheumatoid arthritis despite treatment with disease-modifying antirheumatic drugs (DMARDs).Patients receiving adalimumab 40mg every other week in combination with methotrexate (Anti-TNF Research Study Program of the Monoclonal Antibody Adalimumab [ARMADA] and DE019 trials) or standard antirheumatic therapy (Safety Trial of Adalimumab in Rheumatoid Arthritis [STAR] trial) for 24–52 weeks had significantly higher American College of Rheumatology (ACR) 20, ACR50, and ACR70 response rates than patients receiving placebo plus methotrexate or standard antirheumatic therapy. In ARMADA, an ACR20 response was achieved in 25%, 52%, and 67% of adalimumab plus methotrexate recipients at weeks 1, 4, and 24, respectively. In ARMADA and DE019, improvements in the individual components of the ACR response were significantly greater with adalimumab 40mg every other week plus methotrexate than with placebo plus methotrexate.Monotherapy with adalimumab 40mg every other week was associated with significantly higher ACR20, ACR50, and ACR70 response rates than placebo, as well as significantly greater improvements in the individual components of the ACR response.ACR responses were sustained with adalimumab according to the results of extension studies in which patients received adalimumab in combination with methotrexate (up to 30 months) or as monotherapy (up to 5 years).In both concomitant therapy and monotherapy trials, adalimumab was associated with significantly greater improvements from baseline in health-related quality of life (HR-QOL) measures than placebo; adalimumab also retarded the radiographic progression of structural joint damage to a significant extent compared with placebo.Adalimumab was generally well tolerated as both concomitant therapy and monotherapy. In ARMADA, there were no significant differences between adalimumab and placebo (in combination with methotrexate) in the incidence of adverse events; however, in STAR, the incidence of injection site reactions, rash, and back pain was significantly higher with adalimumab than with placebo (in combination with standard antirheumatic therapy). No cases of tuberculosis were reported in either trial.In conclusion, subcutaneous adalimumab in combination with methotrexate or standard antirheumatic therapy, or as monotherapy, is effective in the treatment of adults with active rheumatoid arthritis who have had an inadequate response to DMARDs. Adalimumab has a rapid onset of action and sustained efficacy. The drug also retards the progression of structural joint damage, improves HR-QOL, and is generally well tolerated. Thus, adalimumab is a valuable new option for the treatment of DMARD-refractory adult rheumatoid arthritis.

ISSN:1173-8804    

出版商:ADIS    

年代:2004

数据来源: ADIS