Hybrid-Primed Lymphocytes and Hybrid Vaccination Prevent Tumor Growth of Lewis Lung Carcinoma in Mice

Abstract

Dendritic cell (DC)-tumor cell hybrids are currently being evaluated as a novel antitumor vaccination strategy. We have explored in an animal model whether administration of DCs fused with poorly immunogenic carcinoma cells could elicit an antitumor response. Fusion of C57/BL6 mice bone marrow-derived DCs with Lewis lung carcinoma (LLC1) cells resulted in approximately 50% fusion efficiency. Hybrid cells (HCs) were used to explore 3 potential tumor therapy strategies: protective immunization, vaccination, and adoptive cellular therapy. Immunization with HCs induced activation of proliferating cytotoxic T cells, upregulation of distinct cytokines genes, and a significant retardation of tumor growth. Similar results were observed by vaccination with HCs in the tumor-bearing host. Finally, when T cells from HC-vaccinated mice were transferred into naive tumor-bearing mice, tumor growth was strongly retarded and an efficient proliferative and cytotoxic T-cell response was observed. Tumor growth was reduced by more than 50%, and tumor development was significantly delayed. Taken together, we demonstrate that HCs offer effective immunotherapy of poorly immunogenic carcinomas. This is independent of whether the HCs are taken for adoptive transfer or as a vaccine.