Overcoming the immunologic response to foreign enzymes in cancer therapy

Foreign enzymes play a part in a variety of cancer treatments and have the potential for a much greater role. In most cases, repeated administration of the enzyme is required for effective therapy, however, this can be restricted by undesirable effects caused by immunogenicity. Repeated or prolonged treatment can lead to an antibody response, and this may neutralize the enzyme and prevent it from remaining in the circulation. Ultimately, this can lead to a diminished therapeutic effect and increase the risk of infusion reactions. More insidiously, there is a danger that antibodies will not only neutralize the foreign enzyme, but will crossreact with a vital component in normal tissue. Such responses can damage normal tissues and give rise to serious clinical syndromes. The aim for enzymes in cancer therapy is to allow repeated treatments without compromising safety or efficacy. This can potentially be achieved by understanding and controlling the immune response and by modifying the enzyme accordingly. A crucial requirement, and one that is particularly challenging for enzymes to achieve, is that the modifications introduced do not interfere with structure, function or stability.