Immunotherapy for Malignant Melanoma using Dendritic Cells

Background: Malignant melanoma is a potentially lethal cancer that arises from melanocytes present in skin, mucosa, or the epithelial surfaces of eyes and ears, and its incidence has increased substantially. Although primary tumor excision can sometimes achieve complete remission, most melanomas are beyond surgical margins when diagnosed, and are usually resistant to chemotherapy and radiotherapy. Therefore, many other therapeutic modalities are being investigated, and one of them is dendritic cells (DC)-based immunotherapy. Objective: The purpose of this study was to investigate the therapeutic effect of DC-based immunotherapy on malignant melanoma. Methods: Malignant melanoma was induced in mice by subcutaneously inoculating B16F10 cell line, and fifteen mice were divided into 3 groups: 1) PBS-treated (n=5), 2) treated with DC (n=5), and 3) treated with tumor lysate (Ag)-pulsed DC (n=5). We identified that DC were able to present Ag to T cells with mixed lymphocyte reaction and induce Ag-specific immune response with delayed hypersensitivity. To evaluate the therapeutic effect, we examined changes of tumor size and survival rates. Results: The following results were obtained: 1. Ag-pulsed DC generated much T cell proliferation (mixed lymphocyte reaction). 2. Ag-pulsed DC treatment induced only delayed hypersensitivity. 3. Ag-pulsed DC treatment decreased tumor size (PBS:703+/-49 mm3, DC:619+/-26 mm3, and Ag-pulsed DC: 463+/-25 mm3) and increased survival rates. Conclusion: Our results suggest that intratumoral injection of Ag-pulsed DC could be used to treat malignant melanoma.ope