Toxicological testing of monoclonal antibodies

Toxicity studies with monoclonal antibodies for in vivo diagnostic or therapeutic administration must be designed case by case to take into account the intended use in humans and the type of structure (nude or coupled to immunotoxins or radionuclides). The design of experiments is influenced by the origin of the clone (murine or human with different problems of antigenicity) and the type of culture (ascites or fermentation with various kinds of possible contaminations). Therefore, routine animal tests must be supplemented by analytical procedures and assays of pharmacological quality control (pyrogenicity, abnormal toxicity). The antigenicity of these antibodies for experimental animals imposes restrictions concerning duration of experiments and extrapolation of the results to humans. Selection of appropriate species is difficult, they should have identical target cells if possible. Sometimes the choice is limited to non-human primates. Toxicological experiments should be based on pharmacokinetic studies. Formal tests on mutagenicity, teratogenicity and cancerogenicity are, in most cases, irrelevant. Antibody formation may make it impossible to carry out longer-term studies.