Highly Potent Immunotoxins Targeting the Membrane-distal N-lobe of GPC3 for Immunotherapy of Hepatocellular Carcinoma.

ABSTRACT: Glypican-3 (GPC3) has become a compelling target for immunotherapy of hepatocellular carcinoma, including antibody-drug conjugate (ADC), and ADC-like immunotoxin. To investigate the impact of epitopes on the potency of ADCs, current study generated a large panel of chicken monoclonal antibodies (mAbs) that targeted 12 different and over-lapping epitopes on GPC3. These mAbs demonstrated a very high affinity with K_d values in the range of 10^-9-10^-14 M, and the highest affinity (K_d value of 0.0214 pM) was 40-fold higher than the previously generated high-affinity mAb YP7 (K_d value of 0.876 nM). Additionally, these mAbs exhibited excellent thermostability with T_m values in the range of 45-82 °C. As a proof-of-concept study for A

SUBMITTER: Li J 

PROVIDER: S-EPMC8899386 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature