1. Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma
- Author
-
Boudewijn E. C. Plaat, Bert van der Vegt, Kirsten L. Moek, Marcel A. T. M. van Vugt, Saskia H Hanemaaijer, Stephanie E van Gijn, Jan L. N. Roodenburg, Ed Schuuring, Bernard F. A. M. van der Laan, Rudolf S N Fehrmann, Sjoukje F. Oosting, University of Zurich, Fehrmann, Rudolf S N, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), and Man, Biomaterials and Microbes (MBM)
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Immunoconjugates ,10039 Institute of Medical Genetics ,GLYCOPROTEIN NONMETASTATIC B ,MELANOMA ,chemistry.chemical_compound ,0302 clinical medicine ,AURISTATIN-E CONJUGATE ,1306 Cancer Research ,Epidermal growth factor receptor ,Antibody-drug conjugates ,Aged, 80 and over ,Membrane Glycoproteins ,Tissue microarray ,biology ,3504 Oral Surgery ,Middle Aged ,Immunohistochemistry ,Oncology ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,PHASE I/II ,2730 Oncology ,Female ,Oral Surgery ,SENSITIVITY ,Glembatumumab vedotin ,Adult ,Antibody-drug conjugate ,610 Medicine & health ,GPNMB ,03 medical and health sciences ,Antigens, Neoplasm ,medicine ,Humans ,BREAST-CANCER ,RNA, Messenger ,RECURRENCE ,Aged ,THERAPEUTIC TARGET ,Squamous Cell Carcinoma of Head and Neck ,business.industry ,Gene Expression Profiling ,CD44 ,Functional genomic mRNA profiling ,Head and neck squamous cell carcinoma ,medicine.disease ,Head and neck squamous-cell carcinoma ,body regions ,030104 developmental biology ,chemistry ,GLEMBATUMUMAB VEDOTIN ,Cancer research ,biology.protein ,570 Life sciences ,business - Abstract
Background: For patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) palliative treatment options that improve overall survival are limited. The prognosis in this group remains poor and there is an unmet need for new therapeutic options. An emerging class of therapeutics, targeting tumor-specific antigens, are antibodies bound to a cytotoxic agent, known as antibody-drug conjugates (ADCs). The aim of this study was to prioritize ADC targets in HNSCC.Methods: With a systematic search, we identified 55 different ADC targets currently targeted by registered ADCs and ADCs under clinical evaluation. For these 55 ADC targets, protein overexpression was predicted in a dataset containing 344 HNSCC mRNA expression profiles by using a method called functional genomic mRNA profiling. The ADC target with the highest predicted overexpression was validated by performing immunohistochemistry (IHC) on an independent tissue microarray containing 414 HNSCC tumors.Results: The predicted top 5 overexpressed ADC targets in HNSCC were: glycoprotein nmb (GPNMB), SLIT and NTRK-like family member 6, epidermal growth factor receptor, CD74 and CD44. IHC validation showed combined cytoplasmic and membranous GPNMB protein expression in 92.0% of the cases. Strong expression was seen in 65.9% of the cases. In addition, 86.5% and 67.7% of cases showed >= 5% and > 25% GPNMB positive tumor cells, respectively.Conclusions: This study provides a data-driven prioritization of ADCs targets that will facilitate clinicians and drug developers in deciding which ADC should be taken for further clinical evaluation in HNSCC. This might help to improve disease outcome of HNSCC patients.
- Published
- 2018