PMID- 15235387 OWN - NLM STAT- MEDLINE DCOM- 20050304 LR - 20191108 IS - 1524-9557 (Print) IS - 1524-9557 (Linking) VI - 27 IP - 4 DP - 2004 Jul-Aug TI - Comparative analysis of antigen loading strategies of dendritic cells for tumor immunotherapy. PG - 265-72 AB - 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. FAU - Shimizu, Keiji AU - Shimizu K AD - Center for Surgery Research, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. FAU - Kuriyama, Hideyuki AU - Kuriyama H FAU - Kjaergaard, Jorgen AU - Kjaergaard J FAU - Lee, Walter AU - Lee W FAU - Tanaka, Hiroshi AU - Tanaka H FAU - Shu, Suyu AU - Shu S LA - eng GR - R01 CA084110/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunother JT - Journal of immunotherapy (Hagerstown, Md. : 1997) JID - 9706083 RN - 0 (Antigens) RN - 0 (Cancer Vaccines) RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Antigen Presentation/immunology MH - Antigens/*immunology MH - Cancer Vaccines/immunology MH - Cell Fusion MH - Cells, Cultured MH - Dendritic Cells/*immunology MH - Female MH - Immunotherapy/*methods MH - Interferon-gamma/metabolism MH - Interleukin-10/metabolism MH - Lymphocyte Activation/immunology MH - Mice MH - Mice, Inbred BALB C MH - Neoplasms/*immunology/pathology/*therapy MH - T-Lymphocytes/metabolism EDAT- 2004/07/06 05:00 MHDA- 2005/03/05 09:00 CRDT- 2004/07/06 05:00 PHST- 2004/07/06 05:00 [pubmed] PHST- 2005/03/05 09:00 [medline] PHST- 2004/07/06 05:00 [entrez] AID - 00002371-200407000-00002 [pii] AID - 10.1097/00002371-200407000-00002 [doi] PST - ppublish SO - J Immunother. 2004 Jul-Aug;27(4):265-72. doi: 10.1097/00002371-200407000-00002.