Evaluation of immunogenicity of recombinant human serum albumin in cynomolgus
Objective:To examine the characteristics of anti-drug antibodies(ADA)produced by cynomolgus after administration of recombinant human serum albumin(rHSA)and compare the differences in ADA characteristics of rHSA and human plasma-derived albumin(pHSA).Methods:A total of 24 cynomolgus were used in a single dose trial,6 animals in each group.Cynomolgus received 1 g·kg-1 pHSA,and 0.3,1 or 2 g·kg-1 rHSA by intravenous injection.Repeated dosing trial was conducted using 12 cynomolgus,6 animals in each group,and they received 1 g·kg-1 pHSA or 1 g·kg-1 rHSA daily by intravenous injection for 6 days.ADA was measured before and at 14 d,21 d,28 d,42 d,and 56 d after drug administration.Results:All animals in both trials were ADA-positive.In the single dose trial,ADA was detectable 14 days(50％positive rate)after administration with pHSA,the positive rate peaked 28 days after dosing(83％),and ADA persisted up to 56 days in some animals.ADA was detectable 14 days after administration with rHSA,and the positive rate peaked 28 days after dosing(positive rate up to 100％)and then began to decrease.In the repeated dosing trial,ADA was detectable 14 days after administration with pHSA and rHSA,and the positive rates all reached a peak(83％)and decreased after 42 days.After single administration of equal doses(1 g·kg-1)of pHSA and rHSA,the rate of antibody positivity induced by rHSA was less than that of pHSA.After repeated administration of equal doses(1 g·kg-1)of pHSA and rHSA,the positivity rates were the same,but the positivity rate of rHSA decreased more rapidly.Conclusion:Both rHSA and pHSA could induce humoral immune responses in cynomolgus,and repeated dosing induced stronger immune responses.
recombinant human serum albuminimmunogenicityanti-drug antibodiescynomolguschemiluminescence immunoassay
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