Monoclonal Antibodies Against PCDH7 for Therapeutic and Diagnostic Use

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated deaths worldwide. UTHealth researchers discovered that the cell surface protein Protocadherin 7 (PCDH7) is highly expressed in NSCLC and promotes lung cancer development. Inventors at UTH in collaboration with Dr. O’Donnell’s group at UTSW have discovered a panel of PCDH7-targeting monoclonal antibodies (mAbs), which exhibited therapeutic potentials. The high affinity anti-PCDH7 mAbs inhibit downstream MAPK pathway activation and suppress tumor growth in mouse tumor models.

Background

NSCLC is the most common lung cancer subtype and remains the leading cause of cancer associated deaths worldwide. Patients have few therapeutic options, and disease progression is inevitable, underscoring the critical need for the identification of new targets and therapeutic approaches to treat this disease.

Significance and Impact

UTHealth researchers identified a critical oncogenic role of PCDH7, which is 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. Therefore, they created anti-PCDH7 mAbs and demonstrated that PCDH7 blockade is a promising therapeutic strategy for lung adenocarcinoma.

Technology Highlights

• Depletion of Pcdh7 reduces lung tumor burden and prolongs survival in mouse models of high-grade NSCLC.
• Anti-PCDH7 mAbs exhibits high specificity and affinity for the PCDH7 extracellular domain.
• Anti-PCDH7 mAbs reduced tumor growth in multiple mouse models. The anti-tumor efficacy in different mouse models were also evaluated.
• Humanized anti-PCDH7 mAbs exhibited antibody dependent cellular cytotoxicity (ADCC) and Fc-mediated immune effector killing of tumor cells in humanized mice.

Potential Applications

The discoveries of PCDH7’s oncogenic role in NSCLC provide an important step towards the clinical development of anti-PCDH7 mAbs for the treatment of NSCLC and other types of tumor with high PCDH7 expression.

Related Publication

Poster at CPRIT conference.

Intellectual Property Status

Patent filed

Available for licensing.

Inventors: Dr. Zhiqiang An and Dr. Ningyan Zhang at UTHealth; and Dr. Kathryn O'Donnell-Mendell at UT Southwestern Medical Center.