Effects of anti CD3 monoclonal antibody on immunity and gene expression profiles of cynomolgus monkeys / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effects of anti CD3 monoclonal antibody (Ant-CD3 McAb) on immune function in cynomolgus monkeys, using the traditional immunotoxicity assessment methods and T cell dependent antibody response (TDAR) test, microarray, etc, and further explore the mechanism of Ant-CD3 McAb. METHODS: Eighteen Cynomolgus monkeys were individually dosed with saline, 0.5 and 2.5 mg·kg-1Ant-CD3 McAb for 7 d. The clinical observation, body weight, hematological test, antibody detection, TDAR test, lymphocyte subsets, bone marrow, histopathological examination and whole blood gene expression profile analysis were evaluated. RESULTS: Ant-CD3 McAb significantly inhibited the immune response to keyhole limpet hemocyanin (KLH) in cynomolgus monkey, and caused the decrease of peripheral white blood cell counts and CD3+ cells, the decrease of lymphocytes in thymus cortex. Microarray test showed that the gene function of differently expressed genes mainly involved in cell proliferation, immune response, cytokine secretion, apoptosis etc. CONCLUSION: Ant-CD3 McAb could induce obvious immunosuppression effects in cynomolgus monkeys. Detection of gene expression profile of whole peripheral blood is feasible in immunotoxicity evaluation. The apoptosis induction and proliferation inhibition of T lymphocytes might be the main cause of the decreased T lymphocytes. IL-8 might play an important role in the mechanism of Ant-CD3 McAb.