Definition

A double recombinant oncolytic vaccinia virus (VV; VACV) genetically engineered to express the human immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential oncolytic, immunostimulating and antineoplastic activities. The double-recombinant VV-GMCSF-Lact contains deletions of viral thymidine kinase (TK) and growth factor (GF) gene fragments in the regions of which the genes of GM-CSF and the oncotoxic protein lactaptin are inserted, respectively. Upon intra-tumoral administration, the double recombinant vaccinia virus VV-GMCSF-Lact specifically infects and replicates in tumor cells causing viral-mediated tumor cell lysis. The released virus particles, in turn, infect and replicate in neighboring tumor cells. Tumor antigens released from the lysed tumor cells also activate the immune system to induce a tumor-specific systemic immune and cytotoxic T-lymphocyte (CTL) response, thereby killing nearby non-infected tumor cells. In addition, VV-GMCSF-Lact promotes the secretion of lactaptin and GM-CSF. Lactaptin is a fragment of human milk kappa-casein (residues 57–134) that further induces the apoptotic death of cancer cells . GM-CSF secreted by the tumor cells attracts dendritic cells (DCs) and may further stimulate a CTL-mediated immune response against tumor cells.