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Radioimmunotherapy of Solid Tumors: Searching for the Right Target

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Radioimmunotherapy of solid tumors remains a challenge despite the tremendous success of 90Y ibritumomab tiuxetan (Zevalin) and 131I Tositumomab (Bexxar) in treating non-Hodgkin's lymphoma. For a variety of reasons, clinical trials of radiolabeled antibodies against solid tumors have not led to responses equivalent to those seen against lymphoma. In contrast, promising responses have been observed with unlabeled antibodies that target solid tumor receptors associated with cellular signaling pathways. These observations suggest that anti-tumor efficacy of the carrier antibody might be critical to achieving clinical responses. Here, we review and compare tumor antigens targeted by radiolabeled antibodies and unlabeled antibodies used in immunotherapy. The review shows that the trend for radiolabeled antibodies under preclinical development is to also target antigens associated with signaling pathways that are essential for the growth and survival of the tumor.

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Keywords: 131I tositumomab; 51 integrin; Bevacizumab; Bexxar; Carbonic Anhydrase Isotype IX; Carcinoembryonic Antigen; Cetuximab; DNA single strand breaks; DNA/histone H1 Associated Protein; Doxorubicin; Epidermal Growth Factor; Filgrastim; Ganglioside 2; Hepatocyte Growth Factor Receptor; Ketoconazole; Labetuzuma; Melanin; Mesenchymal Epithelial Transition Factor; Mucin 1; Panitumumab; Prostate-Specific Membrane Antigen; Radioimmunotherapy; Rituximab; Tenascin-C; Tositumomab; Trastuzumab; Tumor Associated Glycoprotein; Zevalin; anti-neuropilin; antibody dependent cellular cytotoxicity; antigen; complement dependent cytotoxicity; double strand breaks; epidermal growth factor-like domain 7; lymphoma; non-Hodgkins; radioimmunotherapy; radiolabeled antibody; relative biological effectiveness; solid tumor; tumor endothelial marker 1; v3 integrin; vincristine

Document Type: Research Article

Publication date: January 1, 2011

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  • The aim of Current Drug Delivery is to publish peer-reviewed articles, short communications, short and in-depth reviews in the rapidly developing field of drug delivery. Modern drug research aims to build in delivery properties of a drug at the design phase, however in many cases this ideal cannot be met and the development of delivery systems becomes as important as the development as the drugs themselves.

    The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance.

    The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.
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