title: CCL21 (SLC) improves tumor protection by a DNA vaccine in a Her2/neu mouse tumor model.
abstract: Secondary lymphoid-tissue chemokine (SLC/CCL21) is a CC chemokine that is constitutively expressed in various lymphoid tissues and binds to chemokine receptor CCR7 on mature dendritic cells (DCs) and distinct T-and B-cell sub-populations. In vivo, CCL21 regulates the encounters between DC and T cells and thus is a key regulator of adaptive immune responses. We asked whether CCL21 is able to augment immunogenicity of a DNA-based vaccine against Her2/neu in a Balb/c mouse model with syngeneic Her2/neu+ tumor cells (D2F2/E2). Mice were vaccinated intramuscularly with plasmid DNA (pDNA) on day 1 and boosted on day 15; tumor challenge was performed subcutaneously on day 25. Coexpression of CCL21 and Her-2/neu resulted in induction of a TH1-polarized immune response and substantial improvement of the protective effect of the DNA vaccine. Coexpression of tumor antigen pDNA(Her2/neu) with both pDNA(GM-CSF) and pDNA(CCL21) as adjuvants led to further improvement of protection by the vaccine (70% tumor-free mice on day 35 vs 40% with either adjuvant alone vs 5-10% with tumor antigen alone). Our results show that CCL21 is a potent adjuvant for DNA vaccination, particularly in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Clinical use of a pDNA(Her2/neu/CCL21/GM-CSF) vaccine might be particularly promising in minimal residual Her2/neu+ breast cancer.
authors: Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Campus Berlin-Buch and Campus Virchow-Klinikum, Berlin, Germany.
authors: T
authors: T
authors: Nguyen-Hoai
authors: G
authors: G
authors: Baldenhofer
authors: M S
authors: MS
authors: Sayed Ahmed
authors: M
authors: M
authors: Pham-Duc
authors: M D
authors: MD
authors: Vu
authors: M
authors: M
authors: Lipp
authors: B
authors: B
authors: Dörken
authors: A
authors: A
authors: Pezzutto
authors: J
authors: J
authors: Westermann
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D045744:Cell Line, Tumor; D054421:Chemokine CCL21 / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
chemical_list: D019496:Cancer Vaccines; D054421:Chemokine CCL21; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA