Countering immunotoxin immunogenicity
Abstract
The entry of antibody-based drugs into mainstream medicine has provided the oncologist with new therapeutic tools that have begun to transform the treatment of cancer (Scott et al, 2012; Lee et al, 2013). Toxicity profiles and cell killing mechanism(s) exhibited by antibody and small-molecule cytotoxic therapies are largely non-overlapping, thus providing positive clinical advantages relating to drug resistance and therapy side effects. Additionally, in some instances, combinations of antibody given together with conventional chemotherapy show synergistic activity manifest as significant improvements in treatment outcomes (Hallek et al, 2010). However, not all naked antibodies possess therapeutic activity per se, a property that is determined in part by the antibody's particular target molecule. In instances where the antibody has only weak or no observable therapeutic activity, the strategy has been to ‘arm' the antibody with a protein toxin or a highly potent small-molecule cytotoxic drug to create two closely related classes of therapeutic, namely immunotoxins (IT) and antibody drug conjugates, respectively (Kreitman, 2006; Lambert, 2013).
Immunogenicity presents challenges for all antibody-based therapies where multiple administrations of drug over a protracted period are required to achieve a therapeutic effect (Kuus-Reichel et al, 1994). Immunogenicity in this context is defined as the property of the therapeutic to elicit an unwanted immune response when the patient's…
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