Two Novel Human Anti-cd25 Antibodies With Antitumor Activity Inversely Related to Its Affinity and in Vitro Activity

Abstract

\n High tumor regulatory T (Treg) cell infiltration is associated with poor prognosis of many cancers. CD25 is highly expressed on tumor Treg cells and is a potential target for Treg deletion. Previously characterized anti-CD25 antibodies appear to have limited efficacy. Here we identified two human anti-CD25 antibodies, BA9 and BT942, which demonstrated strong tumor growth inhibition in both early and late-stage animal cancer models. BT942 had weaker binding and cytotoxic activity to human CD25-expressing cell lines than BA9. But BT942 showed a stronger anti-tumor effect and resulted a higher expansion of CD8+ T cells and CD4+ T cells in tumor microenvironment at the mouse MC38 model compared to BA9. As CD25 is transiently expressed on activated Teff cells, it is likely that BT942 with lower affinity can distinguish high expression Treg and low expression Teff and therefore cannot kill Teff cells effectively. Such a combination of BT942’s abilities may underline its stronger effect. BT942 also demonstrated higher tumor growth inhibition in combination with an anti-PD1 antibody. Pharmacokinetic tests of BT942 in cynomolgus monkey demonstrated a half-life of 206.97±19.03 hours. No toxicity efficacy was seen in mice efficacy or monkey examinations. BT942 appears to be an excellent candidate for cancer immunotherapy.