Delivery of CXCL9/10/11 plasmid DNAs promotes the tumor-infiltration of T cells and synergizes with PD1 antibody for treating lung cancer

Abstract

Background: Immune checkpoint blockade (ICB)-based cancer immunotherapy presents promising efficacy in cancer treatment. However, only a small portion of patients show responsiveness to the treatment, which is partially caused by limited tumor infiltration of T cells. Chemokines CXCL9, CXCL10 and CXCL11 bind to their receptor CXCR3 to regulate T cell invasion. Methods: We delivered plasmids encoding CXCL9, CXCL10 and CXCL11 to tumor cells and tumor tissues using nanoparticles and investigated their effect on T cell invasion and infiltration. In addition, we applied these nanoparticles together with anti-PD-1 antibody, which is known to activate T cells and restore immune function against tumor cells. The anti-tumor effects were evaluated. Results: Delivering plasmids encoding CXCL9, CXCL10 and CXCL11 by nanoparticles resulted in expression of these chemokines in both LLC cells and tumors. Expressing CXCL9, CXCL10 and CXCL11 promoted the infiltration of T cells in vitro and in vivo, as well as decreased the tumor size. Nanoparticles together with anti-PD-1 displayed the best anti-tumor effects. Conclusions: Delivery of CXCL9/10/11 plasmids by nanoparticles promoted T cell infiltration in tumors and synergizes with the activity of anti-PD1 antibody.