76. Guide Adoptively Transferred T Cells Migrating Into and Killing Tumors With an HSV-2 Based Oncolytic Virus

Adoptive T-cell therapy has shown promises for cancer treatment. However, for treating solid tumors, there is a need for improving the ability of the adoptively transferred T cells to home into and expand in tumors. We explored the possibility of using our developed oncolytic virus FusOn-H2, derived from HSV-2, to induce high levels of local chemo-attractants for the improvement of migration of adoptively transferred T cells and tumor inhibition. In a xenograft animal model, mice bearing PancO2-H7-OVA tumors received an intratumoral injection of FusOn-H2 (1X107 pfu), followed by an intravenous injection of OT-1 cells, which contain a T cell receptor specific to OVA antigen. For imaging and tracing T cell homing to and expanding in the tumor, OT-1 cells were transduced with retroviruses carrying luciferase gene. Our data showed that intratumoral administration of this virus could indeed induce high levels of local chemokine release which were specific attractants for T cells migration, like CXCL9 and CXCL10, and other inflammatory chemokines such as CCL2, CCL3, CCL4 and CXCL1. This chemokine profile really improved the migration of the adoptively transferred T cells to the treated tumor, with a 14-fold increase of T cell tracking in the tumor compared to mock-treatment, based on the luciferase activity in tumors. Moreover, once attracted to the tumor site by the virus, T cells could persist and expand in the tumor for a month without diminishing, significantly longer and more than in mock-treated tumor. These virus induced high chemokines and improved homing of T-cell to the tumor also led to a significantly enhanced therapeutic effect, with a profound inhibition on the tumor growth and even 40% tumor eradication. Our data suggest that HSV-2 based virotherapy combined with adoptive T-cell therapy can potentiate their therapeutic effect against solid tumors that are otherwise difficult to be managed with either treatment alone.