Expert opinion on biological therapy
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Expert Opin Biol Ther · Nov 2007
ReviewReview of hepatitis B surface antigen-1018 ISS adjuvant-containing vaccine safety and efficacy.
Existing hepatitis B virus (HBV) vaccines produce seroprotective titers in > 90% of healthy adult recipients following 3 doses administered over 6 months. The durability of this response is variable. Vaccine efficacy is greatly diminished in immune compromised patients. ⋯ Dynavax's hepatitis B virus vaccine HEPLISAV is comprised of 1018 ISS mixed with recombinant hepatitis B surface antigen. Clinical trials, to date, have shown that HEPLISAV produces rapid, high titer, sustained seroprotection in healthy adults and vaccine hyporesponsive populations. Although additional supporting data are required, this represents a promising strategy to facilitate worldwide HBV prevention efforts.
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Expert Opin Biol Ther · Nov 2007
ReviewDrotrecogin alpha (activated): the treatment for severe sepsis?
Severe sepsis is common and increasing in incidence. Mortality rates remain high. Discovery of the link between the coagulation system and the inflammatory response to sepsis led to the development of drotrecogin alpha (activated). ⋯ Drotrecogin alpha (activated) is associated with an increased risk of bleeding. Recent studies have shed light on its mode of action, which is primarily attributed today to cytoprotective effects especially on the endothelium with improved microcirculation. Ongoing studies will help define which patients are most likely to benefit, perhaps with the help of biochemical markers.
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Expert Opin Biol Ther · Oct 2007
ReviewImatinib mesylate in the treatment of hematologic malignancies.
The treatment of hematologic malignancies has been based for many years on chemotherapy and possibly, for the more aggressive forms, stem cell transplantation. In 2001, the signal transduction inhibitor 571 (STI571, imatinib mesylate) was reported to have striking effects in chronic myeloid leukaemia patients. Since then, imatinib became the first molecular-targeted agent approved for the treatment of human cancer and was later on demonstrated to be effective in other malignancies, such as Philadelphia positive acute lymphoid leukemia, hypereosinophilic syndromes, gastrointestinal stromal tumours and more recently, systemic mastocytosis and other myeloprolipherative disease-carrying platelet-derived growth factor receptor abnormalities. In this article, the authors review the evidence which led to imatinib approval in the treatment of several of the above mentioned diseases.
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Expert Opin Biol Ther · Jun 2007
ReviewEffects of anticoagulant strategies on activation of inflammation and coagulation.
Acute inflammatory events, such as those that occur in sepsis, lead to dysregulation of the coagulation cascade. The hemostatic imbalance in sepsis, characterized by the excessive activation of procoagulant pathways and the impairment of anticoagulant activity, leads to disseminated intravascular coagulation and results in microvascular thrombosis, tissue hypoperfusion and, ultimately, multiple organ failure and death. ⋯ This review summarizes the available experimental and clinical data regarding the interaction between coagulation and inflammation, focusing on the two anticoagulants which are in clinical use, antithrombin and activated protein C. Identification of the different biological mechanisms of the two endogenous anticoagulants might help to determine target patient populations as well as to develop new anticoagulant analogs that differ in there respective effects in coagulation and inflammation.
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Expert Opin Biol Ther · Jun 2007
ReviewPotential of oligonucleotide-mediated exon-skipping therapy for Duchenne muscular dystrophy.
Many of the mutations associated with Duchenne muscular dystrophy can potentially be rescued by exon-skipping therapy, targeting selected exons of prespliced mRNA for the dystrophin gene with antisense oligonucleotides, thereby restoring reading frames. The recent development of antisense oligonucleotides with higher stability and lower toxicity, such as morpholinos, has made it possible to restore dystrophin efficiently in dystrophic mice in vivo with no obvious side effects. There seems little doubt that such exon-skipping therapy is destined to proceed to the clinical application stage in patients with Duchenne muscular dystrophy. ⋯ At present, this multi-exon skipping strategy is being investigated in dystrophic dogs as well as dystrophic mice. There are several challenges that still need to be overcome, including the low uptake of antisense oligonucleotides into the heart and the need to design efficient, nontoxic, cost-effective oligonucleotides. This review summarizes recent progress in exon-skipping therapy and discusses future perspectives with regard to human clinical trials.