title: CCL4 as an adjuvant for DNA vaccination in a Her2/neu mouse tumor model.
abstract: Chemokines are key regulators of both innate and adaptive immune responses. CCL4 (macrophage inflammatory protein-1β, MIP-1β) is a CC chemokine that has a broad spectrum of target cells including immature dendritic cells, which express the cognate receptor CCR5. We asked whether a plasmid encoding CCL4 is able to improve tumor protection and immune responses in a Her2/neu+ mouse tumor model. Balb/c mice were immunized twice intramuscularly with plasmid DNA on days 1 and 15. On day 25, a tumor challenge was performed with 2 × 10(5) syngeneic Her2/neu+ D2F2/E2 tumor cells. Different groups of mice were vaccinated with pDNA(Her2/neu) plus pDNA(CCL4), pDNA(Her2/neu), pDNA(CCL4) or mock vector alone. Our results show that CCL4 is able to (i) improve tumor protection and (ii) augment a TH1-polarized immune response against Her2/neu. Although Her2/neu-specific humoral and T-cell immune responses were comparable with that induced in previous studies using CCL19 or CCL21 as adjuvants, tumor protection conferred by CCL4 was inferior. Whether this is due to a different spectrum of (innate) immune cells, remains to be clarified. However, combination of CCL19/21 with CCL4 might be a reasonable approach in the future, particularly for DNA vaccination in Her2/neu+ breast cancer in the situation of minimal residual disease.
authors.affiliation: Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Virchow, Berlin, Germany.|Max Delbrück Center for Molecular Medicine, Berlin, Germany.|Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Buch, Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Nguyen-Hoai
authors.affiliation: Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Virchow, Berlin, Germany.|Max Delbrück Center for Molecular Medicine, Berlin, Germany.|Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Buch, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Pham-Duc
authors.affiliation: Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Virchow, Berlin, Germany.|Max Delbrück Center for Molecular Medicine, Berlin, Germany.|Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Buch, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gries
authors.affiliation: Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Virchow, Berlin, Germany.|Max Delbrück Center for Molecular Medicine, Berlin, Germany.|Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Buch, Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Dörken
authors.affiliation: Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Virchow, Berlin, Germany.|Max Delbrück Center for Molecular Medicine, Berlin, Germany.|Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Buch, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Pezzutto
authors.affiliation: Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Virchow, Berlin, Germany.|Max Delbrück Center for Molecular Medicine, Berlin, Germany.|Department of Hematology, Oncology, and Tumor Immunology, Charit-University Medicine Berlin, Campus Buch, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Westermann
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D054407:Chemokine CCL4 / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D006801:Humans; D007114:Immunization; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D010957:Plasmids / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D047368:Tumor Burden; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D054407:Chemokine CCL4; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA