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Monoclonal antibodies targeting PCDH7 inhibit tumor growth and enhance targeted therapy response in non-small cell lung cancer

GSE235391 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2026/04/30 Platform GPL16791
Summary
We identified a critical oncogenic role for Protocadherin 7 (PCDH7), a cell surface protein and member of the Cadherin superfamily in NSCLC. PCDH7 is frequently overexpressed in lung adenocarcinoma (LUAD) and associates with poor clinical outcome. Depletion of Pcdh7 reduces lung tumor burden and prolongs survival in mouse models of high-grade NSCLC, demonstrating that this protein is an actionable therapeutic target. Here we report the development and characterization of high affinity anti-PCDH7 monoclonal antibodies (mAbs) that inhibit downstream MAPK pathway activation and suppress tumor growth in multiple mouse models, including KRAS- and EGFR-mutant models. A lead mAb (mAb7) sensitized tumors to the FDA-approved MEK inhibitor trametinib. Moreover, the humanized mAb7-IgG1 exhibited antibody dependent cellular cytotoxicity (ADCC) and Fc-mediated immune effector killing of tumor cells in vivo. These findings provide an important step towards the clinical development of PCDH7-targeting antibodies for the treatment of NSCLC and other tumor types with high PCDH7 expression.
Published in
Monoclonal antibodies targeting PCDH7 inhibit tumor growth and enhance immune responses in KRAS-mutant non-small cell lung cancer
Novaresi N, Ghosh P, Thomas-Jardin S et al. · Science advances 2026 · PMID 42234744 · doi:10.1126/sciadv.aeb0794
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Also filed as BioProject PRJNA985780 and SRA study SRP444878. Searching any of these in the dataset finder brings you back here.

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