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Pharmacokinetics of Monoclonal Antibodies

Implications for Their Use in Cancer Therapy

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Summary

Antibody-targeted therapy of cancer has significantly improved the selective delivery of antitumour agents, either directly or indirectly, but major problems still remain in the form of poor tumour localisation, toxicity to normal tissues and immunogenicity of either the antibody itself or the targeted therapeutic moiety. Modern technology has created engineered antibodies, with the desired characteristics of high selectivity, affinity, avidity and penetration, which promise a way of reducing these problems, while advances in radiobiology have widened the choice of suitable radioisotopes. However, it is becoming evident that efficient therapy will generally require either enhancement of the therapeutic effect, such as the amplification seen with antibody-directed enzyme prodrug therapy (ADEPT) and the multiphase targeting systems, or a combination of different moieties.

The abnormal tumour vasculature creates hypoxia, making cells resistant to therapy, and this was previously seen as a disadvantage to antibody delivery and treatment. However, new combined treatments are now allowing it to be exploited for therapeutic gain. This destruction of the tumour vasculature has the potential to kill many more cells than direct targeting to the tumour cells themselves, so enhancing the treatment. Another form of combined treatment is the use of antibody cocktails which can address tumour heterogeneity by targeting several different antigens. These advances are permitting the development of novel antibody therapies that can be custom designed for the pharmacokinetics required, and should significantly enhance the successes already being reported in this field.

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  1. CRC Targeting and Imaging Group, Department of Clinical Oncology, Royal Free Hospital School of Medicine, Rowland Hill Street, London, NW3 2PF, England

    R. Barbara Pedley

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Pedley, R.B. Pharmacokinetics of Monoclonal Antibodies. Clin. Immunother. 6, 54–67 (1996). https://doi.org/10.1007/BF03259352

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