oncolytic HSV-1 expressing IL-12 and IL-15/IL-15-receptor alpha VG2025

An oncolytic herpes simplex virus type 1 (oHSV-1) genetically engineered to express the human immunostimulating cytokine interleukin (IL)-12 and a complex of the immunostimulating cytokine IL-15 and its receptor alpha unit (IL-15Ra), with potential immunostimulatory and antineoplastic activities. Upon intratumoral administration, oHSV-1 expressing IL-12 and IL-15/IL-15Ra VG2025 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, oHSV-1 expressing IL-12 and IL-15/IL-15Ra VG2025 promotes the secretion of IL-12 and IL-15/IL-15Ra complex by the tumor cells locally in the tumor microenvironment (TME). IL-12 promotes the activation of natural killer (NK) cells, which induces both the secretion of interferon-gamma and a CTL response against the tumor cells. IL-15 stimulates the proliferation of NK cells, CTLs and memory T cells, which induces an anti-tumor immune response. IL-15Ra complexed with IL-15 increases IL-15 signaling and IL-15 half-life upon expression. These actions of the cytokines may increase tumor cell killing and decrease tumor cell proliferation.