oncolytic vaccinia virus expressing anti-CTLA-4 antibody and GM-CSF BT-001

An oncolytic vaccinia virus (VV; VACV) genetically engineered to express 4-E03, an immunoglobulin G1 (IgG1) antibody directed against the human inhibitory T-cell-expressed receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4;CTLA4) and the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential oncolytic, immunostimulating and antineoplastic activities. Upon intra-tumoral administration, the oncolytic VV expressing anti-CTLA-4 antibody and GM-CSF BT-001 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, oncolytic virus BT-001 promotes the secretion of anti-CTLA-4 antibody 4-E03 and GM-CSF by the tumor cells. GM-CSF attracts dendritic cells (DCs) and may further stimulate a CTL-mediated immune response against tumor cells. Anti-CTLA-4 antibody 4-E03 targets and binds to CTLA-4 expressed on T-cells, and inhibits the CTLA-4-mediated downregulation of T-cell activation. This enhances the CTL-mediated immune response against tumor cells. CTLA-4, an inhibitory receptor and member of the immunoglobulin superfamily (IgSF), plays a key role in the downregulation of the immune system.