Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma

Saskia H Hanemaaijer; Stephanie E van Gijn; Sjoukje F Oosting; Boudewijn E C Plaat; Kirsten L Moek; Ed M Schuuring; Bernard F A M van der Laan; Jan L N Roodenburg; Marcel A T M van Vugt; Bert van der Vegt; Rudolf S N Fehrmann

doi:10.1016/j.oraloncology.2018.03.005

Data-Driven prioritisation of antibody-drug conjugate targets in head and neck squamous cell carcinoma

Oral Oncol. 2018 May:80:33-39. doi: 10.1016/j.oraloncology.2018.03.005. Epub 2018 Mar 27.

Affiliations

¹ University of Groningen, University Medical Center Groningen, Department of Otorhinolaryngology/Head and Neck surgery, Groningen, The Netherlands.
² University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Groningen, The Netherlands.
³ University of Groningen, University Medical Center Groningen, Department of Pathology, Groningen, The Netherlands.
⁴ University of Groningen, University Medical Center Groningen, Department of Oral and Maxillofacial Surgery, Groningen, The Netherlands.
⁵ University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Groningen, The Netherlands. Electronic address: r.s.n.fehrmann@umcg.nl.

PMID: 29706186
DOI: 10.1016/j.oraloncology.2018.03.005

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.

Keywords: Antibody-drug conjugates; Functional genomic mRNA profiling; Head and neck squamous cell carcinoma; Immunohistochemistry.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antigens, Neoplasm / immunology
Female
Gene Expression Profiling
Head and Neck Neoplasms / drug therapy*
Head and Neck Neoplasms / genetics
Head and Neck Neoplasms / metabolism
Humans
Immunoconjugates / immunology
Immunoconjugates / therapeutic use*
Male
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism
Middle Aged
RNA, Messenger / genetics
Squamous Cell Carcinoma of Head and Neck / drug therapy*
Squamous Cell Carcinoma of Head and Neck / genetics
Squamous Cell Carcinoma of Head and Neck / metabolism

Substances

Antigens, Neoplasm
GPNMB protein, human
Immunoconjugates
Membrane Glycoproteins
RNA, Messenger