Prevention of immune responses to human erythropoietin in cynomolgus monkeys (Macaca fascicularis)

Genes and proteins of human origin are often administered to monkeys for research purposes, however, it can be difficult to obtain sufficient levels of the products in vivo due to immunological clearance. In this study, we showed that human erythropoietin (hEPO) induces generation of anti-hEPO antibody in cynomolgus macaques (n=2), although 92% of amino acid residues are common between the human and macaque EPO. The administered hEPO was thus eliminated from the animals. On the other hand, when an immunosuppressant, cyclosporin A (CyA), was administered (6 mg/kg) intramuscularly every other day in combination with hEPO (n=2), no anti-hEPO antibody was generated and high serum levels of hEPO were obtained during administration of hEPO, resulting in an increase in serum hemoglobin levels. No adverse effects associated with CyA were observed. Thus, CyA treatment is useful for prevention of immune responses associated with the administration of human proteins in monkeys.