Dendritic cells in models of tumor immunity. Role of Flt3 ligand.
Cancer immunotherapy might be based on the administration to cancer patients of dendritic cells (DC) 'pulsed' with tumor-specific antigens. An alternative approach is to directly expand and/or activate DC in vivo using the cytokine Flt3 Ligand (FL). In mice, FL can drive large expansion of both lymphoid-related DC that appears to selectively enhance Th1-like immune responses and myeloid-related DC that enhances a more mixed Th phenotype. Immunization of FL-treated mice with a protein antigen leads to increased production of antibodies specific for that protein as well as to antigen-specific helper T cell responses. Studies of mouse tumor models have demonstrated that FL administration leads to the generation of protective anti-tumor immune responses, these effects being mediated by CTL and/or NK cells. When, FL has only minor or short term effects, the anti-tumor response can be significantly amplified by adding other cytokines, known to act at the T cell level, such as CD40 ligand (CD40L) or 4-1BBL, a TNF family member. Thus, combination of FL + CD40L or FL + 4-1BBL have superior anti-tumor effects vs. either cytokine alone. In conclusion, cytokines offer a variety of novel approaches for the treatment of cancer, infectious or auto-immune diseases.
Maliszewski
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Immunex Corporation, 51 University Street, Seattle, WA 98101-2936, USA.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D023201:CD40 Ligand / Q000276:immunology / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008565:Membrane Proteins / Q000276:immunology* / Q000627:therapeutic use; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D008565:Membrane Proteins; C084881:flt3 ligand protein; D023201:CD40 Ligand