The Assessment of Stress in Cynomolgus Monkeys

Non-human primates(NHP) are increasingly being used as a non-rodent animal model during preclinical safety evaluation on the basis of proven suitability and comparability between NHP and humans. The introduction of humanised and fully human antibodies imposes further demands on NHP models since many biopharmaceuticals do not interact with rodent or other non-rodent receptors but frequently only cross react with primate tissue. The cynomolgus monkey (Macaca fascicularis) is the preferred NHP model used in routine safety evaluation of biopharmaceuticals. Currently many protocols using the NHP call for the evaluation of changes in lymphocyte subpopulations of both peripheral blood and lymphoid tissue using flow cytometry as well as the standard immunological endpoints. However, there is a high degree of inter- and intra-group variability in lymphocyte marker cell counts in NHP studies and this is often attributed to ‘stress’. Given the restricted supply and relatively small numbers of animals used in these studies, it is critical to gain a clear understanding of the changes that occur in animals during the period before dosing commences in order to establish a clear baseline against which to identify possible effects of the test substance. In this study an assessment of immune phenotype marker baseline data from over 450 animals was undertaken focusing on factors that have been implicated as stressors for primates (e.g. type of caging). Analysis of these data will establish an indication of the factors that potentially could influence the immune status of cynomolgus monkeys.