Pharmacokinetics and safety of an engineered anti-feline PD-1 chimeric antibody following repeated intravenous and subcutaneous administration in healthy cats.

Immune checkpoint inhibitors targeting programmed cell death-1 (PD-1) represent a promising strategy in feline oncology. We previously developed an anti-feline PD-1 monoclonal antibody and engineered an effector-silent variant, 1A1-2-fIgG1-M2, to abolish cytotoxic functions. However, the safety profile and plasma pharmacokinetics (PK) of anti-feline PD-1 antibodies remain uncharacterized. This study aimed to evaluate the safety and PK profiles of 1A1-2-fIgG1-M2 in healthy cats to support its clinical translation. Cats received 1A1-2-fIgG1-M2 intravenously (IV; 3 or 10 mg/kg) or subcutaneously (SC; 3, 7, or 10 mg/kg) every 2 weeks for five doses, or saline as control (n = 3/group). Clinical signs, hematology, serum biochemistry, and necropsy findings were evaluated over 70 days. Anti-idiotype monoclonal antibodies were generated to establish an anti-idiotype antibody-based capture ELISA for plasma drug quantification. While IV groups displayed predictable elimination, SC groups exhibited marked PK variability at 3 and 10 mg/kg. Conversely, the 7 mg/kg SC group (SC-7) consistently maintained stable plasma concentrations (10-80 µg/mL). No mortality, severe adverse events, or acute infusion reactions were observed during the study period. Anti-idiotype ELISA provided robust PK quantification. Repeated SC administration at 7 mg/kg every 2 weeks maintained measurable plasma concentrations and was generally well tolerated in this small exploratory study. This regimen provides a foundation for clinical trials in cancer-bearing cats.