Definition

A genetically modified oncolytic virus (OV) composed of CF33, a replication competent orthopoxviral chimera that is engineered to express the tumor-associated antigen (TAA) CD19, with potential oncolytic, immunostimulating and antineoplastic activities. CD19-expressing OV CF33 is used in combination with certain anti-CD19 agents, such as anti-CD19 chimeric antigen receptor (CAR) T cells or anti-CD19 bispecific antibodies. Upon intratumoral (IT) or intravenous (IV) administration of CD19-expressing OV CF33, the oncolytic virus specifically binds to, infects and replicates in tumor cells, leading to 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, the CD19 antigen expressed by the OV is specifically delivered to and produced in the infected tumor cells. As CD19 is presented on the tumor cell surface, the tumor cells are tagged with CD19. This allows, upon the administration of certain agents that target CD19, the specific eradication of CD19-expressing tumor cells.