Efficacy of immunotherapy approaches in metastatic and non-metastatic lung cancer models

Abstract

Abstract Lung cancer is the leading cause of cancer related deaths accounting for approximately 30% of all cancer related mortalities affecting both men and women. Currently, there is no cure for the common non-small cell lung cancer (NSCLC) thus development of efficacious therapies is urgently needed. In this study, we investigate the efficacy of tumor membrane-based vaccine immunotherapy and immune checkpoint blockade antibodies in an aggressive, non-metastatic, immune checkpoint inhibitor resistant lung cancer model (LL/2) and a highly metastatic lung cancer (CMT-167) model. LL/2 and CMT-167 tumor tissues were harvested from C57BL/6 mice and processed to generate tumor membrane vesicles (TMVs). TMVs were then mixed with adjuvants and used for immunization in conjunction with immune checkpoint inhibitors. Tumor growth was monitored every 3 days. Survival was assessed using a Kaplan-Meier survival curve and significance determined using a Log-rank test for comparison analysis. Metastasis of CMT-167 was assessed by clonogenic assay. TMV alone, or in combination with adjuvants, anti-PD-1 or anti-CTLA-4 antibodies neither decreased the tumor growth nor improved the survival of mice challenged with LL/2 tumor cells. However, anti-PD-1 antibody delayed the tumor growth, improved the survival and reduced pulmonary metastasis in mice challenged with CMT-167 tumor cells. These models provide a valuable tool in analyzing the mechanism of interaction of immune cells with tumors that lead to either tumor regression or resistance to immunotherapies.