Definition

A recombinant oncolytic adenovirus, controlled by synthetic gene circuit, encoding the human immunostimulating factor cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), with potential immunostimulating and antineoplastic activities. Upon administration, the recombinant human GM-CSF-encoding oncolytic adenovirus SynOV1.1 selectively targets, infects and replicates in tumor cells expressing the tumor-associated antigen (TAA) alpha-fetoprotein (AFP), thereby expressing GM-CSF and inducing tumor cell lysis. The lysis of cancer cells causes the release of cancer-specific antigens, and triggers systematic anti-tumor immune responses. In addition, GM-CSF attracts dendritic cells (DCs) and may further stimulate a cytotoxic T-cell response against tumor cells, which results in immune-mediated tumor cell death. The gene circuit contains a synthetic sensory switch that is under the control of a cancer-specific AFP promoter and multiple microRNA inputs. The gene circuits are triggered to activate viral replication and express hGM-CSF in AFP-expressing cancer cells, but not in normal cells.