Preparation and preliminary stability study of tumor microenvironment-responsive PD-L1 antibody-drug conjugates with different drug-antibody ratios
REN Yule
GUO Qingcheng
PAN Zhiyuan
ZHU Weifan
ZHUANG Huangzhen
GAO Tianyu
CHEN Yi
GUO Menghui
LIU Tao
WANG Chenguang
JI Lusha
QIAN Weizhu
HOU Sheng
LI Jun
SUN Ziqiao
WANG Xuekun
XIE Lei
XU Jin
ZHANG Dapeng
GUO Huaizu
Abstract：The rapid development of PD-1/PD-L1 immune checkpoint inhibitors has revolutionized cancer therapy,yet challenges persist in enhancing their therapeutic efficacy.Antibody-drug conjugates(ADC)have the potential to significantly expand the therapeutic window of chemotherapy agents while synergisti-cally activating immune responses.However,the drug-antibody ratio(DAR)may affect key attributes such as activity and stability.To date,research on next-generation PD-L1-targeted ADC with varying DAR values remains limited.In this study,we first developed tumor microenvironment-responsive PD-L1 ADC with different DAR values using various anti-PD-L1 antibodies.These conjugates were subjected to preliminary characterization,activity evaluation,and stability analysis.Our findings demonstrate that both the antibody type and DAR significantly influence the activity and stability of PD-L1 ADC.The de-velopment of next-generation PD-L1 ADC requires a comprehensive consideration of efficacy,drugability,and other factors.This study provides crucial experimental evidence and conceptual frameworks for the ra-tional design and mechanistic exploration of PD-L1-targeted ADC.
Keywords：PD-1/PD-L1 immunotherapyantibody-drug conjugates(ADC)drug-antibody ratio(DAR)tumor microenvironment-responsivestabilityactivity evaluation
Publication Date：2025-12-31
Online Publishing Date：2026-08-28(First online date of this platform, not the publication date of the document)
Pages：11( 945-955 )