Alphavirus-Based Vaccines

Lundstrom, Kenneth

In a prostate tumor model, VEE particles expressing human prostate-specific membrane antigen (PSMA) showed strong cellular and humoral immunity after subcutaneous administration [100] . Furthermore, VEE particles have been employed for the expression of the predominantly prostate tissue-specific six transmembrane epithelial antigen of the prostate (STEAP) [101] . Pre-immunization with VEE-STEAP particles induced a specific immune response and significantly prolonged the overall survival of mice bearing TRAMPC-2 tumors. When TRAMP mice were prophylactically immunized with a prostate stem cell antigen (PSCA) DNA plasmid followed by VEE-PSCA particle administration, a specific immune response and anti-tumor protection were observed in 90% of vaccinated animals [102] . Several vaccine studies have targeted brain tumors. For instance, SFV particles expressing endostatin showed a significant reduction of intratumoral vascularization after intratumoral delivery [78] . In another approach, bone-marrow isolated dendritic cells (DCs) were transduced with SFV vectors carrying cytokine genes of specific cDNAs from melanoma and glioma cells [79] . Pre-vaccination with DCs transduced with SFV-based B16 and 203 glioma cDNAs, respectively, resulted in tumor challenge protection and the prolonged survival of tumor-bearing mice. The combination of DCs transduced with SFV-IL-12 particles and systemically administered IL-18 also provided increased survival rates [111] . Moreover, the expression of human melanoma-associated antigen gp100 and IL-18 from a SIN virus DNA vector induced specific anti-tumor CTL responses and provided anti-tumor protection [80] . Vaccination prevented B16-hgp100 tumor formation and demonstrated significant prolongation of survival in mice with established B16-hgp100 tumors.