CBP501 was originally identified as an optimized peptide of TAT-S216A, a G2 checkpoint abrogating peptide, for the activity in reducing G2 population when combined with DNA damaging agents (SK Sha, et al., Mol Cancer Ther 2007). It is currently in clinical trials (B Y Wong, et al., ASCO 2008) Here we describe a novel activity of CBP501 in increasing the cytotoxicity of bleomycin and cisplatin but not other major cytotoxic anti-cancer agents. CBP501 enhanced DNA damage-induced foci-formation and checkpoint signals in bleomycin treated cells. CBP501 also increased the number of cells in G2 phase, as well the platinum concentration, platinum-DNA adducts and checkpoint signals in cisplatin treated cells. These effects of CBP501 were observed in a variety of cancer cell lines, including all four tested malignant pleural mesothelioma cell lines and MIAPaCa2, a pancreatic cancer cell line, but not human umbilical vein endothelial (HUVEC) cells. We further show that CBP501 enhances the in vitro cytotoxicity and in vivo anti-tumor activity of bleomycin and cisplatin. These studies were performed at the expected dose range in human tumors at the recommended dose of CBP501 in phase 1 studies. These findings collectively indicate that CBP501 has substantial potential as an anti-cancer agent in combination with bleomycin and cisplatin.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1823.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO