Preclinical Evaluation of DB-1419, a Novel Bifunctional and Bispecific Anti-B7-H3 × PD-L1 Antibody-Drug Conjugate.

ABSTRACT:

Purpose

We developed a bifunctional B7-H3 × PD-L1-targeting bispecific antibody-drug conjugate (named DB-1419) conjugated with a novel topoisomerase I inhibitor, P1003 (drug-to-antibody ratio, 8), and assessed its preclinical profiles.

Experimental design

The pharmacologic activities of DB-1419 were assessed in multiple cancer cell lines and immunodeficient and immunocompetent cell line-/patient-derived xenograft (PDX) models. The mechanisms of action behind the efficacy, pharmacokinetics in cynomolgus monkeys, and the safety profiles in vitro and in cynomolgus monkeys were also explored.

Results

With high stability in circulation, DB-1419 displayed efficient cellular internalization and trafficked to the lysosome within 48 hours to release the payload P1003. In vitro

SUBMITTER: Li C 

PROVIDER: S-EPMC12351279 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature