Anti-tumor activity of camptothecin analog conjugate of an RSPO4-based peptibody targeting LGR4/5/6 in preclinical models of colorectal cancer.

ABSTRACT:

Background

Antibody-drug conjugates (ADCs) are a significant advancement in targeted cancer therapy, but none are approved for colorectal cancer (CRC). LGR4/5/6, highly expressed in most CRCs, are promising targets. While LGR5-targeting ADCs show strong anti-tumor effects, their efficacy is limited by LGR5 loss in some CRC cells. RSPO4, a natural ligand for LGR4/5/6, binds all three receptors with high affinity. This research develops RSPO4-based peptibody drug-conjugates (PDCs) to simultaneously target LGR4/5/6, offering a novel therapeutic approach for CRC.

Methods

LGR4/5/6 expression in CRCs was analysed using RNA-seq datasets and Western blot. Peptibody binding affinities were measured, conjugated to camptothecin analog, CPT2, and tested for cytotoxicity in CRC cell line

SUBMITTER: Toh Y 

PROVIDER: S-EPMC12478594 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature