Expert opinion on biological therapy
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The epidermal growth factor receptor (EGFR) plays an important role in the carcinogenesis of many human malignancies and is therefore an attractive target against which anticancer therapy may be effective. At present, there are two ways in which this may be achieved clinically: antibodies against EGFR and inhibitors of the EGFR tyrosine kinase. ⋯ Efficacy data for these agents in various human malignancies is presented. Various other agents that are in the early stages of development at present have also been mentioned.
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Paul Erhlich conceived of antibody-based immunotherapy in the nineteenth century. Rituximab, which is a chimeric monoclonal antibody produced by recombinant technology, became the first monoclonal antibody to be approved for haematological malignancies by the US Food and Drug Administration. ⋯ Radioimmunoconjugates are an attractive therapeutic option for lymphomas due to the inherent sensitivity to radiotherapy, the fact that the local emission of ionising radiation by radiolabelled antibodies may kill cells with or without the target antigen in close proximity to the bound antibody, and penetrating radiation may obviate the problem of limited antibody penetration into bulky, poorly vascularised tumours. This paper reviews rituximab, alemtuzumab and gemtuzumab ozogamicin as monoclonal antibody therapies for leukaemias and lymphomas.
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For many years the annual meeting of the American Society of Clinical Oncology (ASCO) has been the premier meeting in clinical oncology, and one that is closely scrutinised by Wall Street and international investors because of the economic significance of cancer therapies to the pharmaceutical and biotechnology industries. The area of biologicals and targeted therapies exploded in the late 1990s after the blockbuster results with the monoclonal antibody rituximab in the treatment of lymphoma. Although historically a somewhat conservative organisation that is still closely tied to classical cytotoxic chemotherapy, ASCO has been able to integrate various areas of biological therapy into its scope of clinical activity. ⋯ There were 10 papers chosen for plenary presentations and many other key papers were presented at other oral abstract sessions and poster discussion session that were organised by tumour type. In addition to key papers submitted by specific tumour type, for this year's meeting there were 103 abstracts published in the session entitled 'Developmental Therapeutics: Immunotherapy', and 218 in the session entitled Developmental Therapeutics: Molecular Targets', for a total of 321 biological therapy abstracts compared with only 125 abstracts for the session entitled 'Developmental Therapeutics: Cytotoxic Therapy'. This meeting review is organised by biotherapy modality rather than tumour type.
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Expert Opin Biol Ther · Jul 2005
ReviewEndogenous morphine: opening new doors for the treatment of pain and addiction.
Nitric oxide (NO) signalling is at the forefront of intense research interest because its many effects remain controversial and seemingly contradictory. This paper examines its role as a potential mediator of pain and tolerance. Within this context discussion covers endogenous morphine, documenting its ability to be made in animal tissues, including nervous tissue, and in diverse animal phyla. ⋯ Importantly, this mu opiate receptor subtype is morphine-selective and opioid peptide-insensitive, further highlighting the presence of morphinergic signalling coupled to NO release. These findings provide novel insights into pain and tolerance as morphinergic signalling exhibits many similarities with NO actions. Taken together, a select morphinergic signalling system utilising NO opens the gate for the development of novel pharmaceuticals and/or the use of old pharmaceuticals in new ways.
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Cell therapy to treat neuropathic pain after spinal cord injury (SCI) is in its infancy. However, the development of cellular strategies that would replace or be used as an adjunct to existing pharmacological treatments for neuropathic pain have progressed tremendously over the past 20 years. The earliest cell therapy studies for pain relief tested adrenal chromaffin cells from rat or bovine sources, placed in the subarachnoid space, near the spinal cord pain- processing pathways. ⋯ These technologies have been modelled with a variety of murine cell lines, derived from embryonic adrenal medulla or CNS brainstem, in which cells are transplanted, which downregulate their proliferative, oncogenic phenotype either before or after transplant. An alternative approach for existing human cell lines is the use of neural or adrenal precursors, in which the antinociceptive properties are induced by in vitro treatment with molecules that move the cells to an irreversible neural or chromaffin, and non-oncogenic, phenotype. Although such human cell lines are at an early stage of investigation, their clinical antinociceptive potential is significant given the daunting problem of difficult-to-treat neuropathic SCI pain.