Monoclonal Antibodies Targeting PCDH7 Inhibit Tumor Growth and Enhance Immune Responses in Kras-Mutant Non-small Cell Lung Cancer

Authors

• Nicole Novaresi
• Poorva Ghosh
• Shayna Thomas-Jardin
• Hui Deng
• Xuejun Fan
• Zhiqiang Ku
• Wei Xiong
• Xiaorong Zhou
• Jingfei Zhu
• Huiyu Li
• Mahesh S Padanad
• Bethany Smith
• Chul Ahn
• John D Minna
• Zhiqiang An
• Ningyan Zhang
• Kathryn A O'Donnell

Language

English

Publication Date

6-5-2026

Journal

Science Advances

DOI

10.1126/sciadv.aeb0794

PMID

42234744

PMCID

PMC13232558

PubMedCentral® Posted Date

6-3-2026

PubMedCentral® Full Text Version

Post-print

Abstract

We identified an important oncogenic role for protocadherin 7 (PCDH7), a cell surface protein frequently overexpressed in lung adenocarcinoma and associated with poor clinical outcome. Pcdh7 depletion reduces tumor burden and prolongs survival in KrasLSL-G12D; Tp53fl/fl mice. These findings nominate this cell surface protein as an actionable therapeutic target and highlight the therapeutic potential of PCDH7 inhibition for non–small cell lung cancer. We report the development and characterization of high-affinity anti-PCDH7 monoclonal antibodies (mAbs) that inhibit downstream mitogen-activated protein kinase (MAPK) pathway activation and suppress tumor growth in multiple mutant KRAS–driven models. A lead mAb (mAb7) sensitized tumors to the US Food and Drug Administration–approved MAPK kinase inhibitor trametinib and the KRASG12C inhibitor adagrasib. A humanized mAb7-IgG1 (Hu-mAb7) exhibited antibody-dependent cellular cytotoxicity and Fc-mediated immune effector killing of tumor cells in vivo. Moreover, a murinized antibody (Ms-mAb7) improved antitumor immunity in a KrasG12D syngeneic tumor model by enhancing infiltration and activation of cytotoxic immune cells. These findings provide an important advance in the clinical development of PCDH7-targeting antibodies for lung cancer treatment.

Keywords

Animals, Cadherins, Humans, Lung Neoplasms, Mice, Proto-Oncogene Proteins p21(ras), Carcinoma, Non-Small-Cell Lung, Antibodies, Monoclonal, Protocadherins, Cell Line, Tumor, Mutation, Cell Proliferation, Pyrimidinones, Pyridones

Published Open-Access

yes

Recommended Citation

Novaresi, Nicole; Ghosh, Poorva; Thomas-Jardin, Shayna; et al., "Monoclonal Antibodies Targeting PCDH7 Inhibit Tumor Growth and Enhance Immune Responses in Kras-Mutant Non-small Cell Lung Cancer" (2026). The Brown Foundation: Institute of Molecular Medicine. 84.
https://digitalcommons.library.tmc.edu/molecular_med/84