Characterization of the Anti-Tumour Immune Response Following Treatment with an Infected Leukemia Cell Vaccine

Abstract

Current treatment methods for Acute Leukemia (AL) only provide temporary therapeutic efficacy as most patients will experience relapse within 2 years following first remission. Our lab has determined that vaccination with autologous cells infected with oncolytic virus MG1 can provide durable cures in a pre-clinical mouse model of AL. However, the mechanism(s) by which the infected cell vaccine (ICV) stimulates T cell dependent anti-tumour immunity and provides protection against tumour growth is unknown. This thesis was aimed to determine 1) what antigen presenting cell populations are activated post ICV immunization and 2) what T cell subsets are important in developing anti-tumour immunity during ICV immunization. My thesis has demonstrated that ICV immunization is more effective at inducing in vivo dendritic cell activation compared to irradiated L1210 cells alone and this activation may be a reason as to why we see improved anti-tumour efficacy in our ICV model. In addition, we have determined that CD4 T cells play an essential anti-leukemic role during ICV immunization and that neutralizing antibody production is a CD4 T cell dependent mechanism. Our data also demonstrates that both CD4 and CD8 T cell populations from ICV immunized mice provide a leukemia-specific anti-tumour immune response. Taken together, this data suggests that CD4 T cells may be acting as helper T cells to aid in the robust activation of leukemia-specific anti-tumour CD8 T cells. Our pre-clinical data characterizing the immune response has improved our understanding of the mechanism(s) which contribute to the efficacy of the ICV and will help provide a rationale framework with which to begin translating this treatment to clinical trials.