628. An Oncolytic Adenovirus Armed with a GM-CSF Activating Designed Zinc-Finger Protein Transcription Factor: A Potential Cancer Vaccine Approach

Abstract

Granulocyte macrophage colony stimulating factor (GM-CSF) is a potent activator of the immune system shown to enhance anti-tumor immune responses. We are inserting engineered zinc-finger protein transcription factors (ZFP TFs) up-regulating the expression of GM-CSF, into selectively-replicating oncolytic viral vectors, such as ONYX-411, in order to render them capable of acting as in vivo vaccines. In this system replication-dependent expression of the encoded ZFP TF transgene restricts expression to the appropriate cancer cells, while viral replication in these tumor cells results in local gene amplification and spread. GM-CSF secretion by infected tumor cells should stimulate an immune response against the tumor-specific antigens generated by the oncolytic action of the virus. This in turn is predicted to prime the immune system to direct the systemic elimination of tumor cells not reached by the armed therapeutic virus itself and thereby enhance its therapeutic efficiency.