Expert opinion on biological therapy
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Chronic pain is often resistant to currently used drugs. The effect of these is frequently self-limiting, with increasing level of side effects caused by increased doses. Biological pain therapies provide a means to target molecules to specific types of neural cells in spatially limited areas. Targeted biological therapies utilize agents acting at specific sites, or virus or cell vectors allowing expression and secretion of transgenic substances in small anatomical compartments. Biological approaches to treatment of chronic pain may be able to provide greater analgesic efficacy, avoiding many of the limitations associated with current analgesics. ⋯ Biological therapy of pain holds great promise and is rapidly developing. Despite the significant numbers of preclinical studies in the last two decades only a single biological agent, the cone snail toxin ziconotide, has been advanced through all stages and licensed for clinical use. Biological therapy of pain is thus here to stay, but will need more substantial proof of efficacy and safety before being widely accepted and routinely used.
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Expert Opin Biol Ther · Jul 2011
ReviewChimeric antigen receptor (CAR)-engineered lymphocytes for cancer therapy.
Chimeric antigen receptors (CARs) usually combine the antigen binding site of a monoclonal antibody with the signal activating machinery of a T cell, freeing antigen recognition from MHC restriction and thus breaking one of the barriers to more widespread application of cellular therapy. Similar to treatment strategies employing monoclonal antibodies, T cells expressing CARs are highly targeted, but additionally offer the potential benefits of active trafficking to tumor sites, in vivo expansion and long-term persistence. Furthermore, gene transfer allows the introduction of countermeasures to tumor immune evasion and of safety mechanisms. ⋯ Because of recent advances in immunology, genetics and cell processing, CAR-modified T cells will likely play an increasing role in the cellular therapy of cancer, chronic infections and autoimmune disorders.
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Alzheimer's disease (AD) is a debilitating neurodegenerative illness affecting over 35 million people worldwide. Solanezumab is a monoclonal antibody that binds to β-amyloid (Aβ), a protein that plays a key role in the pathogenesis of AD. The drug is currently being investigated in Phase III trials as a disease-modifying treatment for AD. ⋯ Solanezumab can neutralize soluble Aβ peptides, which may represent the more neurotoxic of the Aβ species. Phase II findings support the compound's safety, which has been a concern for some Aβ immunotherapies. Cerebrospinal and plasma biomarker changes with solanezumab treatment are encouraging. Results of the ongoing Phase III trials will be instrumental in determining the drug's clinical significance.
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Expert Opin Biol Ther · Jun 2011
Intensive chemotherapy of metastatic colorectal cancer: weighing between safety and clinical efficacy: Evaluation of Masi G, Loupakis F, Salvatore L, et al. Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Lancet Oncol 2010;11:845-52.
This paper evaluates a recent study whereby a four-drug combination regimen adding bevacizumab to triplet fluorouracil, oxaliplatin and irinotecan chemotherapy is described for the first-line treatment of metastatic colorectal cancer. It extends the use of intensive medical treatments combining chemotherapy and the VEGF inhibitor bevacizumab, opening new perspectives for the design of four-drug intensive regimen-associating chemotherapy and targeted agents. In the future, these four-drug intensive regimens should be further improved for efficacy:toxicity ratio and verification in randomized trials.
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Expert Opin Biol Ther · May 2011
Editorial ReviewThe clinical and biological role of CD20 membrane antigen modulation under immunotherapy with anti-CD20 monoclonal antibody rituximab in lymphoprolipherative neoplastic disorders.
Immunotherapy using an antibody (rituximab) targeting CD20 antigen in combination with chemotherapy has been recently associated with significantly improved response rate and survival in patients with various types of CD20-positive B-cell lymphoproliferative disorders. This treatment may induce the disappearance of CD20 surface expression on neoplastic B-cells. Several mechanisms have been proposed to explain CD20 loss after rituximab therapy, while the clinical significance (if any) of this phenomenon is still not clear. We have produced a brief overview of the biological aspects of CD20 modulation after rituximab treatment and its possible clinical implications.