title: CCL19 as an adjuvant for intradermal gene gun immunization in a Her2/neu mouse tumor model: improved vaccine efficacy and a role for B cells as APC.
abstract: The aim of this study was to evaluate the efficacy of the chemokine CCL19 (ELC) as an adjuvant for intradermal gene gun delivery of Her2/neu DNA and to investigate the role of B cells in CCL19-mediated enhancement of immune responses. Balb/c mice were immunized intramuscularly (i.m.) on days 1 and 15 with plasmid DNA (pDNA) (100 μg DNA) or intradermally (i.d.) by gene gun delivery (1-2 μg DNA). Administration of pDNA encoding Her2/neu (pDNA(Her2/neu) was compared with pDNA(Her2/neu) plus pDNA(CCL19), pDNA(CCL19), mock vector or uncoated gold particles/phosphate-buffered saline (PBS). Tumor challenge was performed subcutaneously on day 25 with syngeneic Her2/neu(+) tumor cells (D2F2/E2). Intradermal immunization by gene gun led to an enhancement of tumor protection by the DNA vaccine as compared with i.m. immunization. The protective effect of the vaccine was further enhanced by coadministration of pDNA(CCL19) both after i.m. and i.d. immunization. Tumor protection was associated with Her2/neu-specific T cell and humoral immune responses. Experiments in B-cell-deficient μMT mice showed that B cells are crucial for CCL19-mediated enhancement of tumor rejection, most likely as antigen-presenting B cells. DNA vaccines against Her2/neu may play a future role in the treatment of Her2/neu-positive breast cancer patients in a clinical situation of minimal residual disease.
authors.affiliation: Department of Hematology, Oncology and Tumor Immunology Charité-University Medicine Berlin, Campus Berlin-Buch, Campus Benjamin Franklin and Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Nguyen-Hoai
authors.forename: O
authors.initials: O
authors.lastname: Hohn
authors.forename: M D
authors.initials: MD
authors.lastname: Vu
authors.forename: G
authors.initials: G
authors.lastname: Baldenhofer
authors.forename: M S
authors.initials: MS
authors.lastname: Sayed Ahmed
authors.forename: B
authors.initials: B
authors.lastname: Dörken
authors.forename: S
authors.initials: S
authors.lastname: Norley
authors.forename: M
authors.initials: M
authors.lastname: Lipp
authors.forename: A
authors.initials: A
authors.lastname: Pezzutto
authors.forename: J
authors.initials: J
authors.lastname: Westermann
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D019470:Biolistics / Q000379:methods*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D054415:Chemokine CCL19 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D054415:Chemokine CCL19; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA