Identification of CADM1 as an Immunotherapeutic Target and Evaluation of a Novel CADM1-Targeting Antibody-Drug Conjugate in Preclinical Osteosarcoma Models

Authors

Yifei Wang
Zhongting Zhang
Caterina Longo
Wendong Zhang
Qi Wang
Amer Najjar
Xiangjun Tian
Rossana N Lazcano Segura
Michael E Roth
Jonathan Gill
Douglas J Harrison
Zhaohui Xu
Yanhua Yi
Xin Zhou
Sylvester Jusu
Timothy M Stearns
Steven B Neuhauser
Carol J Bult
Jing Wang
Alexander J Lazar
Richard Gorlick

Language

English

Publication Date

1-10-2026

Journal

Molecular Cancer Therapeutics

DOI

10.1158/1535-7163.MCT-25-0450

PMID

41517891

PMCID

PMC12925509

PubMedCentral® Posted Date

2-23-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Due to the paucity of validated cell surface osteosarcoma-specific targets, patients with this condition have long been excluded from the benefits of antibody-drug conjugate (ADC) therapy observed in patients with several solid and hematologic malignancies. Our comprehensive surfaceome profiling approach previously identified osteosarcoma-specific cell-surface antigens that are highly expressed in osteosarcomas but minimally expressed in normal tissues. As a result, one such antigen, CADM1, was selected for the generation of an ADC. We tested a CADM1-targeting ADC with a tesirine payload (SG3249) in vitro in osteosarcoma, rhabdomyosarcoma, and neuroblastoma patient-derived xenograft cell lines. In vivo, we tested six CADM1-expressing osteosarcoma patient-derived xenograft models. The CADM1 ADC demonstrated significant antitumor activity in vitro across the osteosarcoma, rhabdomyosarcoma, and neuroblastoma cell lines. Additionally, it effectively reduced tumor volume and extended event-free survival in all six osteosarcoma PDX models tested. Notably, the CADM1 ADC achieved a major complete response in one model (OS2), complete responses in two models (OS1 and OS33), and partial responses in three models (OS9, OS17, and OS31). Based on these results, clinical development of CADM1-targeted therapies for osteosarcoma and other CADM1-expressing pediatric solid tumors may be warranted.

Published Open-Access

yes

Recommended Citation

Wang, Yifei; Zhang, Zhongting; Longo, Caterina; et al., "Identification of CADM1 as an Immunotherapeutic Target and Evaluation of a Novel CADM1-Targeting Antibody-Drug Conjugate in Preclinical Osteosarcoma Models" (2026). Faculty, Staff and Student Publications. 6063.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6063