Full Name
Shae Komant
Job Title
Graduate Student
Company
University of Alberta
City (Work Address)
Edmonton
State/Province/County (Work Address)
AB
Abstract Title
Genetically Engineered Vaccinia Virus Expressing MHC-I as a Precision Medicine Melanoma Vaccine.
Abstract Summary
Oncolytic viral therapy is a novel treatment strategy that selectively infects and kills cancer cells and induces an anti-tumor immune response. The ability of current oncolytics to stimulate anti-tumor responses varies, therefore novel means of inducing immune activity is necessary. Vaccinia virus (VAC) is a promising oncolytic candidate due to its safety profile, easily manipulatable genome, and ability to induce a potent immune response. Here, we investigated the use of a modified VAC (VAC SCT-CD80), that encodes a major histocompatibility complex-I presenting the chicken ovalbumin protein, OVA, as a single chain trimer (SCT) with or without the costimulatory molecule CD80. To determine if VAC SCT-CD80 can induce an antigen specific immune response we infected murine B16F10 melanoma cells and co-cultured the infected tumor cells with OT-1 T-cells. Three days post co-culture, T cells expressed activation markers and proliferated. We next determined if infection of B16F10 cells in vivo could induce an antigen specific response and lead to tumor regression. OT-1 T-cells were adoptively transferred pre-tumor implantation and following tumor establishment, VAC variants were administered. We observed the presence of previously activated OT-1 T-cells in the tumor and spleen following VAC SCT-CD80 or VAC SCT treatment. All VAC treated groups showed slowed tumor growth. These data highlight the potential to generate a VAC stimulated immune response by intra-tumoral delivering of a defined peptide-MHC. This ability to bolster a T-cell response using viruses is an important step for the advancement of immunotherapies and supports the use of VAC as a vaccine platform.