oncolytic adenovirus expressing interferon beta/CD40 ligand MEM-288

A conditionally replicative, oncolytic adenovirus that has been genetically engineered to encode the transgenes for the human cytokine interferon beta (IFN-beta) and MEM40, a recombinant, chimeric form of CD40 ligand (CD40L), with potential immunostimulating and antineoplastic activities. Upon intratumoral administration, the oncolytic adenovirus expressing IFN-beta/CD40L MEM-288 selectively infects and replicates in tumor cells, leading to tumor cell lysis. In addition, the IFN-beta expressed by the oncolytic adenovirus activates T lymphocytes, dendritic cells (DCs) and natural killer (NK) cells, and induces an anti-tumor immune response against the tumor cells. The CD40L expressed by the oncolytic adenovirus specifically binds to and activates CD40, a cell surface receptor that belongs to the tumor necrosis factor (TNF) receptor family and is expressed on various immune cells, such as B lymphocytes, monocytes, and DCs. Activation of CD40 induces proliferation and activation of B lymphocytes, shifts the induction of immunosuppressive macrophages towards immunostimulatory macrophages, activates monocyte-derived DCs (moDCs) and leads to the secretion of inflammatory cytokines. This activates the immune system to mount a cytotoxic T-lymphocyte (CTL) immune response against tumor cells.