Preclinical comparison of prolgolimab, pembrolizumab and nivolumab
Aleksandr Gordeev, Andrei Vaal, Maria Puchkova, Iana Smirnova, Aleksandr Doronin, Anna Znobishcheva, Daria Zhmudanova, Aleksei Aleksandrov, Mikhail Sukchev, Evgeny Imyanitov, V. V. Solovyev, Pavel A. Iakovlev
Abstract
Prolgolimab is a recombinant IgG1-based anti-PD-1 antibody, whose properties were improved by the introduction of the LALA mutation, and which has demonstrated high efficacy in patients with metastatic melanoma. This paper presents the results of comparative preclinical studies of antigen-binding and effector functions involving prolgolimab and conventional IgG4 antibodies, nivolumab and pembrolizumab. None of the studied antibodies had undesirable antibody-dependent cellular cytotoxicity activity. Prolgolimab has shown higher PD-1 receptor occupancy and T-cell activation, but lower propensity to activate antibody-dependent cellular phagocytosis as compared to nivolumab and pembrolizumab. An in vivo study in mice inoculated with CT26.wt cancer cells showed that tumor growth inhibition was 16% for pembrolizumab and 56% for prolgolimab. This study warrants clinical comparison of IgG1- and IgG4-based anti-PD-1 antibodies.