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αvβ6 Integrin Expression In Solid Tumours: A TROCEPT Target for Oncolytic Viral Therapy

T Webb(1) R C Khanolkar(1) S Shareza(1) A T Baker(1) A B Gerry(1) D Krige(1) A L Parker(1,2) D K Cole(1,2)

1:Accession Therapeutics; 2:Cardiff University

Upregulation of various integrins in tumours make them attractive targets for immunotherapeutic agents in cancer. The RGD (Arg-Gly-Asp)-binding integrin, αvβ6, is a cell-surface receptor exclusively expressed on epithelial cells. The major function of αvβ6 integrin is the activation of transforming growth factor-β, with additional roles shown to be involved in cell adhesion and migration and has also been implicated to play a pro-tumorigenic role. However, αvβ6 integrin expression has not been comprehensively studied to determine its frequency, intensity and pattern of expression in a wide range of human tumour indications and healthy tissues.

Here, the expression of αvβ6 integrin was examined across multiple solid tumours and healthy tissues at the gene and protein level. High expression intensity and a high prevalence of positively was observed in multiple tumor types of epithelial cancers including pancreatic, head and neck, bladder, lung, and oesophageal carcinomas. αvβ6 integrin was absent, or expressed weakly, in most adult healthy tissue, with the exception of strong expression in the transitional epithelium of healthy bladder and moderate expression in stomach. Furthermore, expression of αvβ6 integrin was also observed in metastatic lesions.

These data provide a first comprehensive analysis of αvβ6 integrin expression, confirming its presence in the majority of carcinomas, and absence or low expression in most healthy tissues. These data also provide key information for indication selection and a healthy tissue expression profile that should be considered for on-target toxicity for the αvβ6 integrin targeted therapy, TROCEPT, a tumour-specific oncolytic adenovirus platform, heading for clinical trials.

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