Oxidized Mannan-modified Tumor Cells Induced Protective Antitumor Activity

Tumor vaccine has been the focus of resent efforts in the tumor immunotherapy. Antigen-presenting cells (APC) such as dendritic cells (DCs) and macrohages play a vital role in priming antitumor activity. DCs and macrohages express mannose receptors at high level, which facilitate uptake of antigen, and participate in antigen processing for the effective antigen presentation. Targeting mannosylated antigens to APCs via mannose receptor (MR) in vivo and ex vivo has been investigated extensively for its ability to enhance immune responses. It is also notable that tumor antigen modified by oxidized mannan induces potent antigen-specific CTL response in mice.Here, we used the whole tumor cell as antigen resources, modified oxidized mannan to two histologically different tumor cells, LL/2c and CT26, as vaccines and investigated the antitumor response in mice. The vaccination s.c. with oxidized mannan-tumor cells induced protective antitumor responses against their subsequent parental tumor cell challenges.We used the CT26 tumor model to investigated the protective antitumormechanism of oxidized mannan-tumor cells. T cell depletion experiments in vivo showed that tumor rejection depended on both CD8++ T cells and CD4++ T cells. The spleen T cells from mice vaccinated with oxidized mannan-CT26 cells showed CD8+ T cell-mediated tumor-specific cytotoxicity in a 4-h 51Cr release assay. The production of multiple antibody against parent CT26 cell was confirmed by Western Blotting assay. In addition, deposition of immunoglobulins in tumor tissue was found by the direct immunofluorescence assay in mice vaccinated by oxidized mannan-CT26 cells.Taken together, these findings suggested the oxidized mannan-modified tumor cells induced effectively protective antitumor response, as compared with non-modified cell vaccines. The antitumor activity was dependent on both tumor-specific CTL response and production of multiple antibodies.