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Targeting of Drugs 4 pp 81–90Cite as

Advances in Diagnosis and Treatment of Neoplasia Using Radioactive Monoclonal Antibodies

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Part of the book series: NATO ASI Series ((NSSA,volume 273))

Abstract

The immunoglobulin molecule has long been the focus of investigators as a potential diagnostic and therapeutic tool for cancer (Bale et al, 1955). The first preparations of polyclonal antibodies seemed to bear out this possibility (Goldernberg, et al, 1978), however the difficulty in obtaining clinically relevant quantities through experimental animal immunisation protocols that existed and the great variability between preparations (Mach et al, 1980) made the transit from the test-tube to the clinic very difficult. Apart from limited availability, elements of unpredictability and irreproducibility hampered the research progress of cancer immunotherapy. It was the hybridoma technology (Kohler and Milstein, 1975) and the resulting monoclonal antibodies that gave new impetus to medical diagnosis and treatment. There are still however a number of obstacles to be overcome. Absolutely tumour-specific antigens are rare so crossreactivity is a potential problem. Non specific targeting of tissues rich in reticuloendothelial tissue (bone marrow, liver) is of concern. Penetration into solid tumours, due to adverse physiological or anatomical properties, is poor (Jain, 1990). Antibody dilution in the large volume of the human host circulation and shed antigen-antibody complexes may pose further pharmacokinetic problems. A sensitive host immune system is a further impediment as a part from the well characterised response to the murine antibody (HAMA), it can also recognise even relatively small chemical alterations to humanised molecules caused by linkers (Johnson et al,), thus limiting the therapeutic potential of repetitive treatments. Even the use of humanised antibodies repeatedly has been shown to result in the production of anti-idiotype antibodies (Lockwood et al, 1993). Absolute uptake in human cancer is much less than that achieved in murine xenografts (Epenetos et al, 1986). A variety of problems stemming from the actual imaging or therapeutic agents attached to the antibody have also been identified e.g. toxin immunogenicity (Pai et al, 1991),111 In proclivity for the liver (Sands and Jones, 1987).

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Authors and Affiliations

  1. Tumour Targeting Laboratoy, Imperial Cancer Research Fund Oncology Unit, Dept of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, DuCane Rd., London, W12 OHS, UK

    Anthony Maraveyas & Agamemnon A. Epenetos

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  1. Anthony Maraveyas
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  1. Centre for Drug Delivery Research, The School of Pharmacy, University of London, Brunswick Square, London, WC1N 1AX, England, UK

    Gregory Gregoriadis  & Brenda McCormack  & 

  2. SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA

    George Poste

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Maraveyas, A., Epenetos, A.A. (1994). Advances in Diagnosis and Treatment of Neoplasia Using Radioactive Monoclonal Antibodies. In: Gregoriadis, G., McCormack, B., Poste, G. (eds) Targeting of Drugs 4. NATO ASI Series, vol 273. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1207-7_6

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