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 lung cancer models LL/2 and CMT-167 models. LL/2 and CMT-167 tumor tissues were harvested from C57BL/6 mice and processed to generate tumor membrane vesicles (TMVs). TMVs were then modified with immunostimulatory molecules and used for immunization. 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 vaccine alone, or in combination, 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. The prophylactic vaccination of TMV vaccine prevents the CMT-167 tumor growth in mice and helps the mice develop immunological memory to the tumor cell challenge. In a therapeutic setting, the TMV vaccine inhibited tumor growth and induced primary tumor regression in 40% of mice and significantly reduced the metastatic tumor burden. Anti-tumor immunity induced by TMV vaccine requires CD4+ and NK cells albeit to a lesser extent but not CD8+ T cells for controlling the tumor growth. 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.
