Selective Ablation of Malignant Cells using Apoptotic Gene Therapy

While chemotherapy is a key treatment strategy for many solid tumors, it is rarely selective for tumor cells. OncoSenx has developed an effective suicide gene therapy approach to eliminate solid tumors based on their unique sate of transcriptional activation. The p53 tumor suppressor is frequently mutated or dysregulated in cancers and as a result the upstream signaling pathways activating TP53 transcription are strongly upregulated. We exploit this under appreciated feature of the p53 tumor suppressor pathway to target malignant cells. Leveraging the Fusogenix Proteo-Lipid Vehicle platform, a p53-driven inducible suicide gene, iCasp9, is delivered systemically. In malignant cells where the p53 pathway is upregulated the inducible suicide gene is expressed and upon activation with a chemical activator tumor cells rapidly undergo apoptosis eliminating solid tumors. As a single agent our suicide gene therapy out performs checkpoint blockade as a single agent and synergizes in combination with checkpoint blockade to produces curative and durable control of CT26 tumors. Key Take Aways: • Mutation/ablation of the p53 Tumor suppressor results in upregulation the TP53 locus. • An engineeredTP53 promoter can selectively kill malignant cells in vitro and in vivo. • This approach synergizes with checkpoint blockade.