Abstract
Anti-drug antibodies (ADA) are relevant for the safety evaluation of biopharmaceuticals by impacting the toxicokinetic and pharmacokinetic profile, especially in studies of longer duration. For pre- and postnatal studies, both maternal and infant antibodies might be relevant. Whilst much information is available for ADA development in adult animals, little is known for infants. As the drug is present at clonal T cell selection during priming of the developing immune system, it is feasible that the infant immune system recognizes the antigen as “self”. To provide more insight into this, we analyzed ADA data from eight cynomolgus monkey (M. fascicularis) and one marmoset (C. jacchus) studies. In total, 378 maternal animals and 357 infants were analysed. The results showed that there was a significantly (p < 0.001) reduced likelihood of ADA development in infant animals compared to maternal animals, and infants from ADA positive maternal animals had a higher likelihood to develop ADA themselves, compared to infants from ADA negative maternal animals.In conclusion, these data indicate that negative clonal selection of T cells targeting the drug in infant animals does occur and apparently at a higher rate compared to maternal animals. The ADA formation in maternal and infant animals needs further consideration if animals are being re-used in subsequent studies.
