Cmv Gb/Pp65 Evlps Formulated With Gm-Csf As A Therapeutic Vaccine Against Cmv-Positive Tumors

e14032Background: Numerous laboratories have demonstrated cytomegalovirus (CMV) antigens in over 90% of GBM tumors, medulloblastoma and breast cancer. Memory CD4+ and CD8+ T cells are most frequently directed against the gB and pp65 antigens at frequencies that can exceed 10%. Thus, CMV gB and pp65 represent attractive, highly immunogenic “foreign” antigen components of a vaccine against CMV-positive tumors that can exploit high precursor frequencies of CD4+ and CD8+ T cells. Methods: Enveloped virus-like particles (eVLPs) are produced after transfection of HEK 293 cells with a plasmid encoding murine leukemia virus Gag plasmid fused in-frame with CMV pp65 antigen, which gives rise to particles. Co-transfected CMV gB plasmid enables particles budding from the cell surface to incorporate the gB protein into the lipid bilayer. Results: Ex vivo studies using PBMCs from GBM patients demonstrated that gB/pp65 eVLPs restimulate both CD4+ and CD8+ T cells at frequencies comparable to those observed for healthy C...