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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE235391 | GEO | 2024/07/01

REPOSITORIES: GEO

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