Abstract 2850: Demonstration of anti-tumor efficacy in multiple preclinical cancer models using a novel peptide inhibitor (Aurigene-012) of the PD1 signaling pathway

Programmed cell death-1 (PD-1), an immunoreceptor belonging to the CD28 family, plays an important role in negatively regulating immune responses. Blocking of PD-1 signalling pathway has been shown to result in restoration of defective immune cell functions in cancer and chronic infections. PD-1 targeted therapies in the ongoing clinical trials are based on either antibodies or fusion proteins. To exploit unique advantages of peptides over antibodies or fusion proteins towards addressing the limitations of the current clinical candidates, herein we report a peptide based strategy to block the PD-1 signaling pathway. Sequences critical for ligand-receptor interaction were identified and combined in a non-linear fashion. The strategy resulted in a novel peptide, AUR-012 (29-mer), which displayed sub-nanomolar potency in disruption of PD1-PDL1/2 interaction, and highly effective restoration of proliferation and effector functions of splenocytes and PBMCs. In vivo studies demonstrated an excellent PK-PD correlation with sustained PD for >24 h. In preclinical models of melanoma, breast and kidney cancers, AUR-012 showed superior efficacy compared to therapeutic agents currently used in the clinic in inhibition of both primary tumor growth and metastasis. Interestingly, dosing once in three days was equally efficacious as once a day dosing with no signs of overt toxicity and generation of neutralizing activity. These findings support further development of AUR-012 for potential clinical use. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2850. doi:1538-7445.AM2012-2850