Identification of signaling pathways involved in the mechanism of action of the immunomodulatory peptide gamma-D-glutamyl-L-tryptophan.

5591 Background: Gamma-D-glutamyl-L-tryptophan (SCV-07) is being studied for attenuation of oral mucositis (OM) in head and neck cancer patients receiving chemoradiation therapy. In a pilot study SCV-07-treated subjects had delayed onset of ulcerative OM (Adkins 2009) which correlated with changes in circulating cytokines (Alterovitz 2010). In animal studies SCV-07 inhibits growth of different xenografted tumor types. SCV-07 acts via immune modulation; initial evaluation of SCV-07 signaling demonstrated inhibition of cytokine induced STAT3 transcriptional activity. In this study we explored further the molecular mechanisms by which SCV-07 interferes with mucositis pathobiology and concurrently exhibits anti-tumor activity. Methods: Tyrosine phosphorylated STAT3 (STAT3 PY) was evaluated by Western blot of Jurkat or CD45 mutant Jurkat cells with or without IL-10 or IFNα stimulation and SCV-07. Global phosphorylation profiles were analyzed using phosphoprotein detection array kits. C57/B6 mice inoculated wit...