Publications [#151619] of Walter T Lee

Papers Published

1. K Shimizu, H Kuriyama, J Kjaergaard, W Lee, H Tanaka, S Shu, Comparative analysis of antigen loading strategies of dendritic cells for tumor immunotherapy., Journal of immunotherapy (Hagerstown, Md. : 1997), vol. 27 no. 4 (March, 2005), pp. 265-72, ISSN 1524-9557
   (last updated on 2013/05/16)

   Abstract:
   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.

   Keywords:
   Animals • Antigen Presentation • Antigens • Cancer Vaccines • Cell Fusion • Cells, Cultured • Dendritic Cells • Female • Immunotherapy • Interferon-gamma • Interleukin-10 • Lymphocyte Activation • Mice • Mice, Inbred BALB C • Neoplasms • T-Lymphocytes • immunology • immunology* • methods* • pathology • secretion • therapy*