An AI-guided biparatopic DLL3-targeting ADC demonstrates enhanced preclinical efficacy
Presenter: Liang Tian, PhD Session: Antibody-Drug Conjugates 2 Time: 4/22/2026 9:00:00 AM → 4/22/2026 12:00:00 PM
Authors
Chuan Chen , Yue Wu , Chenpeng Su , Zhaohui Chen , Dandan Liu , Jiyuan Tian , Xiaoqian Chen , Yang He , Yongxin Shang , Rongmei Yan , Liang Tian , Jian Peng , Zhenping Zhu Earendil Labs, Wilmington, DE
Abstract
Purpose This study aimed to develop a novel biparatopic antibody-drug conjugate (ADC) targeting delta-like ligand 3 (DLL3) for small cell lung cancer (SCLC) and other neuroendocrine neoplasms, addressing limitations of previous DLL3-targeted therapies. Methods Leveraging our AI-guided antibody development platform, we engineered a biparatopic anti-DLL3 antibody with optimized binding and internalization properties. The antibody was conjugated with various linker-payload combinations. In vitro cytotoxicity of the ADCs were evaluated using DLL3-expressing cell lines and in vivo efficacy were assessed using CDX mice models. Safety was assessed in transgenic mice and non-human primates. Results The biparatopic antibody demonstrated higher internalization efficiency compared to the monoclonal antibody counterparts. The ADC showed potent cytotoxicity across multiple DLL3-expressing cell lines and achieved significant tumor suppression in CDX models. Toxicological studies revealed a favorable safety profile in both transgenic mice and non-human primates. Conclusion This biparatopic ADC represents a promising therapeutic candidate for DLL3-expressing tumors, demonstrating enhanced efficacy and favorable preclinical safety compared to previous approaches.
Disclosure
C. Chen, None.. Y. Wu, None.. C. Su, None.. Z. Chen, None.. D. Liu, None.. J. Tian, None.. X. Chen, None.. Y. He, None.. Y. Shang, None.. R. Yan, None.. L. Tian, None.. J. Peng, None.. Z. Zhu, None.
Cited in
Control: 6819 · Presentation Id: 4293 · Meeting 21436