A fully human antibody that inhibits the integrin avb6 reduces tumour growth and modulates key biomarkers


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Cath Eberlein1, Ian Foltz2, Avril Alfred2, Zhu Cao1, Neil Smith1, Viv Jacobs1, Jaspal Kang2, Steve Powell1, Karen McDaid1, Jane Kendrew1, Simon Barry1

1AstraZeneca, Cheshire, UK, 2Amgen, Vancouver, Canada

Abstract

Increased expression of the integrin avb6 occurs in a number of human cancers including lung, colorectal, breast, head and neck, and prostate cancer. In normal tissues avb6 plays a key role in modulating the activation of latent TGFb, by binding the TGF-b latency associated peptide LAP through the high affinity binding site RGDLxxL. In addition avb6 also binds the extracellular matrix component fibronectin. By binding both latent TGF-b and fibronectin avb6 has the potential to influence tumour growth by activating both TGF-b or classical integrin mediated signalling pathways.