Effect of TPP-26870 amino acid substitutions within each CDR on APC in vitro plasma half-life. APC activity was measured by Pefachrome PCa. (A) APC activity in plasma over a period of 120 minutes in the presence of TPP-26870 V_H variants. (B) APC plasma half-life in the presence of TPP-26870 V_H variants. (C) Effects of V_H amino acid substitutions on APC in vitro plasma half-life and histone H3 cleavage compared with the parental antibody TPP-26870. (D) APC activity in plasma in the presence of TPP-26870 V_L variants. (E) APC plasma half-life in the presence of TPP-26870 V_L variants. (F) Identification of V_L substitutions with prolonged APC in vitro plasma half-life and enhanced APC-mediated H3 cleavage activity. Plasma in vitro half-life assay (n = 3 independent experiments).