alpha V beta 8 antagonist PF-06940434

An antagonist of integrin alpha v beta 8, with potential antineoplastic activity. Upon administration, PF-06940434 selectively binds to and blocks the receptor for integrin alpha v beta 8, thereby preventing integrin alpha v beta 8 binding. This may result in the inhibition of cell adhesion in the tumor microenvironment (TME) and blocks the activation of the cytokine transforming growth factor-beta 1 (TGF-b1), preventing TGF-b1-mediated signal transduction. This abrogates TGF-b1-mediated immunosuppression, enhances anti-tumor immunity in the TME and promotes a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells leading to tumor cell death. This may lead to a reduction in TGF-b1-dependent proliferation of cancer cells. Alpha v beta 8 integrin plays a key role in tumor initiation, growth, and progression through TGF-b1 activation. It is expressed in a variety of tumor cell types and is associated with poor prognosis.