modified vaccinia virus Ankara expressing Flt3L/OX40L MQ710

A recombinant, non-replicative, modified vaccinia virus Ankara (MVA) engineered with the deletion of the vaccinia E5R gene and the expression of two membrane-anchored transgenes, fms-like tyrosine kinase 3 ligand (Flt3L) and OX40 ligand (OX40L), with potential immunostimulatory and antineoplastic activities. Upon intratumoral administration, MVA expressing Flt3L/OX40L MQ710 is transduced into tumor cells and Flt3L and OX40L are expressed. The recombinant MVA, with the deletion of the E5R gene, activates the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway and increases type I interferon (IFN) production. Flt3L binds to the Flt3 tyrosine kinase receptor and promotes Flt3 signaling, thereby expanding the population of antigen-presenting dendritic cells (DCs). OX40L binds to and activates signaling pathways downstream of its cognate receptor, tumor necrosis factor receptor superfamily member 4 (TNFRSF4; OX40), which is expressed on activated T cells and regulatory T cells (Tregs). This causes depletion of OX40-expressing Tregs in the tumor microenvironment (TME) via OX40L-OX40 interaction and is facilitated by the rMVA-induced type I IFN and IFN-I receptor (IFNAR)-mediated signaling. This inhibits Treg-mediated suppression of effector T-cells, induces the proliferation of memory and effector T lymphocytes and increases cytokine production. Altogether, MQ710 promotes immune activation and anti-tumor immune responses.