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

• Published in: Cancer gene therapy Vol. 19; no. 12; pp. 880 - 887
• Main Authors: Nguyen-Hoai, T, Hohn, O, Vu, M D, Baldenhofer, G, Sayed Ahmed, M S, Dörken, B, Norley, S, Lipp, M, Pezzutto, A, Westermann, J
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-12-2012; Nature Publishing Group
• Subjects: 631/1647/2300; 631/250/251/1567; 631/250/590/1991; 692/699/67/1347; Adenomatous polyposis coli; Adjuvants; Animals; Antigen-presenting cells; B-Lymphocytes - immunology; Biolistics - methods; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Vaccines - administration & dosage; Cancer Vaccines - genetics; Cancer Vaccines - immunology; CCL19 protein; Cell Line, Tumor; Chemokine CCL19 - genetics; Chemokine CCL19 - immunology; Chemokine CCL19 - metabolism; Chemokines; Deoxyribonucleic acid; Disease Models, Animal; DNA; DNA vaccines; ErbB-2 protein; Female; Gene Expression; Gene Therapy; Genes; Genetic aspects; Humans; Immune response; Immune response (humoral); Immunization; Injections, Intradermal; Lymphocytes B; Lymphocytes T; Mammary Neoplasms, Experimental - genetics; Mammary Neoplasms, Experimental - immunology; Mammary Neoplasms, Experimental - therapy; Mice; Mice, Inbred BALB C; Minimal residual disease; original-article; Physiological aspects; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - immunology; T-Lymphocytes - immunology; Tumor cells; Vaccine efficacy; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Germany; CCR7; DNA vaccination; CCL19; chemokines; Her2/neu; gene gun
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/cgt.2012.78

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
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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.