Targeted therapy with the antibody-drug conjugate sacituzumab-govitecan as a promising treatment strategy for head and neck squamous cell carcinoma

Introduction Systemic treatment of head and neck squamous cell carcinoma (HNSCC) is based on chemotherapy, anti-PD-1 immunotherapy and EGFR inhibition. New targeted therapies with antibody-drug conjugates (ADC) have improved progression-free and overall survival in other oncological entities, such as the ADC sacituzumab govitecan (SG) directed against the cell surface antigen TROP2 in metastatic triple-negative breast cancer. There is evidence that HNSCC tumors express TROP2 and other ADC targets.

Methods Tissue samples of HNSCC tumors (n=26) and normal adjacent tissue (NAT) (n=11) were analyzed by immunhistochemistry and 8 HNSCC cell lines were examined by flow cytometry for TROP2 expression. The response of these 8 HNSCC cell lines to treatment with SG was examined in vitro using the calorimetric XTT assay. Employing the chicken embryo chorioallantoic membrane assay intravenous treatment and topical treatment with SG was applied to HNSCC xenografts in vivo.

Results The HNSCC tumors showed heterogeneous expression of TROP2, with most having moderate (12 of 26) or strong staining intensity (10 of 26). None of the NAT showed a strong immunohistochemical detection response (0 of 11). In vitro, all HNSCC cell lines responded to treatment with SG. In vivo, SG significantly reduces tumor cell burden and cell proliferation and significantly induces apoptosis in HNSCC xenografts.

Conclusion Since TROP2 is expressed in all examined HNSCC tumors and a clear response of HNSCC cell lines and xenografts to SG treatment was shown in vitro and in vivo, SG appears to be a promising treatment strategy for HNSCC.

 

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Publication History

Article published online:
19 April 2024