756. The Use of Immune Cell Trafficking to Deliver an Oncolytic Virus to Tumors

Abstract

Cytokine Induced Killer (CIK) cells are a population of ex vivo-expanded PBMC's that have been found to target and destroy tumors following systemic delivery. However their effective clinical use is typically limited to residual disease. Oncolytic viruses, modified such that their replication is restricted to tumor cells, have demonstrated antitumor effects in the clinic, even against large primary tumors. It was found that an oncolytic strain of vaccinia virus displayed unusual replication kinetics within CIK cells, with an extended eclipse phase. This period of time between viral infection and lysis correlates well with the time required for CIK cells to traffic to the tumor in vivo. Additionally, CIK cells were found to maintain their killer phenotype while infected, and vaccinia-infected tumor cells were shown to become more susceptible to CIK cell killing (possibly due to NKG2D ligand up-regulation). In vivo studies used whole body bioluminescent and fluorescent imaging to track viral distribution, CIK cell trafficking and tumor size in immunocompetent mouse models. It was found that pre-infected CIK cells could be used to deliver virus systemically to tumors, with minimal infection at other sites in the body. Furthermore, it was shown that pre-infected CIK cells demonstrated significantly increased antitumor effects compared to either therapy alone, or compared to both therapies used in combination. This represents a new approach to combining two biological therapies in order to best harness the benefits of both and to increase their individual potency. This method could potentially further be used to deliver any gene-based therapy to a tumor with subsequent selective replication at the target site.