Comparative Analysis of Antigen Loading Strategies of Dendritic Cells for Tumor Immunotherapy
| Autor: | Keiji Shimizu, Hideyuki Kuriyama, Jorgen Kjaergaard, Suyu Shu, Walter T. Lee, Hiroshi Tanaka |
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| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
T-Lymphocytes medicine.medical_treatment Immunology Antigen presentation Biology Lymphocyte Activation Cancer Vaccines Cell Fusion Interferon-gamma Mice Immune system Antigen Neoplasms medicine Animals Immunology and Allergy Antigens Antigen-presenting cell Cells Cultured Pharmacology Antigen Presentation Mice Inbred BALB C Cell fusion Antigen processing Dendritic Cells Dendritic cell Immunotherapy Interleukin-10 Cancer research Female |
| Zdroj: | Journal of Immunotherapy. 27:265-272 |
| ISSN: | 1524-9557 |
| DOI: | 10.1097/00002371-200407000-00002 |
| Popis: | Dendritic cells (DCs) loaded with antigens can effectively stimulate host immune responses to syngeneic tumors, but there is considerable controversy as to which forms of antigen-loading are most immunogenic. Here, the authors compared immunotherapeutic reactivities of DCs loaded with a variety of antigen preparations. Because DC maturation stages affect their capacities of antigen processing and presentation, two DC populations were used for the current analysis: in vivo Flt-3 ligand-induced mature DCs and in vitro bone marrow-derived DCs, which were less mature. To facilitate a direct comparison, the LacZ gene-transduced B16 melanoma model system was used, where beta-galactosidase served as the surrogate tumor-rejection antigen. DC loading strategies included pulsing with the beta-galactosidase protein, H-2K restricted peptide, tumor cell lysate, and irradiated tumor cells and fusion of DCs with tumor cells. Our results demonstrated that electrofusion of DCs and tumor cells generated a therapeutic vaccine far superior to other methods of DC loading. For the treatment of 3-day established pulmonary tumor nodules, a single intranodal vaccination plus IL-12 resulted in a significant reduction of metastatic nodules, while other DC preparations were only marginally effective. Immunotherapy mediated by the fusion cells was tumor antigen-specific. Consistent with their therapeutic activity, fusion hybrids were the most potent stimulators to induce specific IFN-gamma secretion from immune T cells. Furthermore, fusion cells also stimulated a small amount of IL-10 production from immune T cells. However, this IL-10 secretion was also induced by other DC preparations and did not correlate with in vivo therapeutic reactivity. |
| Databáze: | OpenAIRE |
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