Immunotoxicity testing in nonhuman primates.

Biological relevance is generally the major justification for using nonhuman primates (NHP) during preclinical safety assessment. This holds particularly true for the evaluation of biopharmaceuticals with NHP often being the species of choice. For safety assessment of small molecules, NHP are used in case of a higher degree of metabolic similarity, to detect the highly specific immunotoxic side effects and to discriminate toxicity from efficacy of immunomodulatory drugs. Unlike for rodent immunotoxicity studies, standardized tests and protocols are generally less available for NHP. The immunotoxicity testing protocols described in the present chapter have been adapted for application to NHP samples. In principle, rodent protocols can be transferred to NHP. Fortunately, most of the immunotoxicity parameters delineated in the ICH S8 guideline can be applied to NHP specimens. Exceptions are the host resistance assay and the delayed type hypersensitivity test. Owing to the close structural and physiological similarity between NHP and human, human test kits or reagents are often well suited for application to NHP samples. For data evaluation it should be noted that no inbred strains of NHP are available, resulting in a large inter-animal variability for most immunotoxicity assay results. The experimental protocols and reagents described in this chapter were developed specifically for the cynomolgus monkey (Macaca fascicularis), currently the most commonly used NHP species in toxicology. In many instances, these protocols will also be applicable to rhesus monkeys (M. mulatta) and potentially to other Old World macaques. For the marmoset (Callithrix jacchus), a New World monkey also used in toxicology, the choice of available immunotoxicity testing protocols is much reduced when compared to macaques.