Abstract
Transforming growth factor β (TGF-β) is a multifunctional cytokine that plays crucial pathophysiological roles in various diseases, such as cancer and fibrosis. However, the disease modulation by targeting TGF-β1 isoform remains to be established, regardless of several studies employed with limited antibodies. Here, we developed an RNA aptamer to human active TGF-β1, named APT-β1, and characterized its properties in vitro and in vivo. APT-β1 bound to human and mouse active TGF-β1 proteins with high affinity and specificity and strongly inhibited TGF-β1-induced downstream signaling and cell morphology with 50% inhibition concentration (IC50) values at picomolar concentrations. In a xenograft mouse model of non-small cell lung cancer, APT-β1 alone showed no appreciable effect on tumor growth, while it greatly enhanced the anti-tumor effect of gefitinib, an approved tyrosine kinase inhibitor. These findings strongly suggest that the anti-TGF-β1 medication may be a promising cancer therapy to suppress repopulation of lung cancer in combination with certain anti-cancer drugs, such as gefitinib.