Definition

A genetically modified oncolytic viral strain of the herpes simplex type 1 (HSV-1) virus, expressing the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) and an antibody-like molecule directed against the human inhibitory T-cell-expressed receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4;CTLA4), with potential oncolytic, immunostimulating and antineoplastic activities. Upon administration, the oncolytic HSV-1 expressing anti-CTLA-4 antibody-like molecule and GM-CSF RP2 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. Oncolytic virus RP2 expresses a fusogenic protein, GALV-GP R-, for optimal tumor cell infection and killing. In addition, Oncolytic virus RP2 promotes the secretion of GM-CSF and anti-CTLA-4 antibody-like molecule 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-like molecule targets and binds to CTLA-4 expressed on T cells, and inhibits the CTLA-4-mediated downregulation of T-cell activation. This leads to a 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.