Preclinical characterization of therapeutic antibodies targeted at the carboxy-terminus of Sonic hedgehog

• DOI: 10.18632/oncotarget.24510
• Publication Date: 2018-02-16T05:07:55Z
• Authors: Bhairavi Tolani; Ngoc T. Hoang; Luis A. Acevedo; Etienne Giroux Le...; Hui Li; Biao He; David M. Jablons
• Keywords: Targeted Therapy; Cyclopamine

The Sonic Hedgehog (Shh) signaling pathway has been implicated in the development and tumor progression of a number human cancers. Using synthetic peptide mimics to mount an immune response, we generated mouse mAb carboxy (C)-terminus Shh protein characterized its preclinical antitumor effects. In vitro screening guided selection best candidate for scale-up production therapeutic development. C-term anti-Shh, Ab 1C11-2G4 was selected based on ELISA screens, Western blotting, flow cytometric analyses. Purified shown recognize bind both cell surface Shh. Administration not only reduced viability 7 cancer lines but also significantly inhibitted growth xenograft model A549 lung cells. Ex vivo analyses tumors revealed reduction signal transduction apoptosis 2G4-treated mice. Collectively, our results provide early demonstration utility antibodies specific C-terminal region Shh, support continued evaluate their potential efficacy cancers which activity is elevated.