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IMAGE: Figure 1: Schematic of experimental procedures for generation of novel anti-Sonic Hedgehog (Shh) candidate therapeutic antibodies directed at the carboxy (C)-terminal. (A) Two synthetic peptide mimics of Shh (AA 247-264… view more 

Credit: Bhairavi Tolani, email: Bhairavi.Tolani@ucsf.edu David M. Jablons, email: David.Jablons@ucsf.edu

Even though the Shh pathway is mainly quiescent in adults, the safety of Shh-targeting with therapeutic antibodies was questioned initially because not only does the N-terminus of the Shh protein play an important role in embryonic development, but Shh also plays a poorly understood role in tissue homeostasis and repair in adults.

Furthermore, the research team previously showed that Shh+ cells expressing the full-length protein appeared to provide a signal for proliferation, migration and chemotherapy-resistance properties, making functional targeting of full-length Shh by the use of C-terminus anti-Shh antibodies an attractive therapeutic strategy.

Ex vivo analyses of A549 xenograft tumors from mice treated with the C-terminus Shh antibody Ab 1C11-2G4 provided further support that Shh signal transduction is modestly down-regulated after treatment, as evidenced by suppressed transcript and protein levels of Shh downstream target GLI. Activation of the pathway occurs when Shh binds to its receptor Patched but signaling is inhibited in a small population of

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