Abstract:
:Two methods of using tumour located enzymes have been described. These are antibody directed enzyme prodrug therapy (ADEPT) and macromolecule directed enzyme prodrug therapy (MDEPT), where the tumour located enzyme converts a non-toxic prodrug into a cytotoxic drug at tumour sites. The alternative use of tumour located enzymes is to inactivate rescue agents that protect cells from antimetabolite action, and is described as 'Antimetabolite with inactivation of rescue agent at cancer sites' (AMIRACS). The leakiness of tumour blood vessels and poor lymphatic drainage allows enzymes to be targeted to many cancers by attachment to polymeric macromolecules (MDEPT), as well as to antibodies and antibody fragments (ADEPT). To avoid systemic toxicity, enzyme activity in blood and normal tissues must be very low before giving a prodrug or rescue agent. Antibodies directed against the enzyme component of macromolecular conjugates have proved to be very efficient at clearing normal tissues. Human enzymes which are over expressed by cancer cells can be exploited particularly if they require co-factors or co-substrates, either in situ or targeted to extracellular sites. Bacterial enzymes have advantages in specificity but require some form of immunological control in view of their immunogenicity. Prodrugs which generate drugs with very short half lives are desirable, and have been developed, including one which has a differential toxicity between prodrug and the active drug of 1000 to 10,000 fold. The range of antimetabolites available for AMIRACS was initially restricted to inhibitors of dihydrofolate reductase but has been greatly extended by the introduction of inhibitors of other enzymes. The limitations of these systems are discussed.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Bagshawe KD,Burke PJ,Knox RJ,Melton RG,Sharma SKdoi
10.1517/13543784.8.2.161subject
Has Abstractpub_date
1999-02-01 00:00:00pages
161-72issue
2eissn
1354-3784issn
1744-7658journal_volume
8pub_type
杂志文章abstract::Recombinant toxins constitute a new modality for the treatment of cancer, since they target cells displaying specific surface-receptors or antigens. They are fusion proteins, which contain toxin and ligand regions, and are produced in Escherichia coli. The ligand may be a growth factor or a fragment of an antibody, an...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.9.1405
更新日期:1998-09-01 00:00:00
abstract::Immunosuppressant drugs are crucial in order to protect transplanted kidney, heart or liver against the body's natural defence mechanisms. These drugs are used to prevent both acute rejection of the organ as well as chronic deterioration of the graft over longer periods of time. Currently used immunosuppressant drugs ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.3.295
更新日期:2005-03-01 00:00:00
abstract::Thienopyridines have a well-established role in the treatment of coronary artery disease, especially in the setting of acute coronary syndromes and percutaneous coronary interventions. Ticlopidine, the first FDA-approved thienopyridine, was shown to be effective in reducing coronary events in high risk patients, but t...
journal_title:Expert opinion on investigational drugs
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doi:10.1517/13543780903176415
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abstract:BACKGROUND:Microtubule stabilizing agents such as taxanes are an integral part of therapy for multiple solid tumors. However, due to limitations of these agents, newer more effective cytotoxic agents are necessary. Ixabepilone, an epothilone B analog, is a novel microtubule stabilizing agent. OBJECTIVE:This review pro...
journal_title:Expert opinion on investigational drugs
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abstract::Introduction: Renal cell carcinoma (RCC) consists of distinct clinical and biologic entities, with an urgent need for novel therapies targeting histology-specific molecular drivers of cancer growth. The MET pathway is now being targeted by multiple novel agents in clinical development. This review highlights the upcom...
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.974803
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abstract::The annual meeting of the American Diabetes Association was held in Boston, MA. There were over 6500 participants, one-third from overseas, and 1103 papers were presented. Abstracts from the meeting have been published, from which abstract numbers are given below, e.g., (A141). Considerable progress has been made in u...
journal_title:Expert opinion on investigational drugs
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journal_title:Expert opinion on investigational drugs
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doi:10.1517/13543784.7.11.1795
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journal_title:Expert opinion on investigational drugs
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更新日期:2001-12-01 00:00:00
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journal_title:Expert opinion on investigational drugs
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更新日期:2006-12-01 00:00:00
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journal_title:Expert opinion on investigational drugs
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journal_title:Expert opinion on investigational drugs
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更新日期:2012-05-01 00:00:00
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更新日期:2021-01-04 00:00:00
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pub_type: 社论
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journal_title:Expert opinion on investigational drugs
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.6.987
更新日期:1998-06-01 00:00:00
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更新日期:2008-09-01 00:00:00
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journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
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journal_title:Expert opinion on investigational drugs
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更新日期:2003-05-01 00:00:00
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journal_title:Expert opinion on investigational drugs
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更新日期:1997-07-01 00:00:00
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journal_title:Expert opinion on investigational drugs
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