Definition

An oncolytic vaccinia virus (VV) engineered to express a fusion protein comprised of the metabolic modulator and adipokine leptin and the human cytokine interleukin (IL)-2, with potential oncolytic, immunostimulating and antineoplastic activities. Upon administration, oncolytic VV expressing leptin/IL-2 fusion protein ASP1012 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 cytotoxic T-lymphocyte (CTL)-mediated immune response, thereby killing nearby non-infected tumor cells. In addition, the leptin/IL-2 fusion protein is expressed by the oncolytic VV in infected cancer cells. Leptin may modulate and improve T-cell metabolic function in the tumor microenvironment (TME), and enhance T-cell-mediated anti-tumor immune responses. IL-2 may further stimulate anti-tumor immune responses, thereby increasing tumor cell killing and decreasing tumor cell proliferation.