CCL21 (SLC) improves tumor protection by a DNA vaccine in a Her2/neu mouse tumor model
Autor: | Antonio Pezzutto, Martin Lipp, T Nguyen-Hoai, M D Vu, Bernd Dörken, M S Sayed Ahmed, Gerd Baldenhofer, M Pham-Duc, Jörg Westermann |
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Rok vydání: | 2011 |
Předmět: |
endocrine system
Cancer Research Receptor ErbB-2 medicine.medical_treatment C-C chemokine receptor type 7 Biology Cancer Vaccines HER2/neu DNA vaccination Mice Chemokine receptor Cell Line Tumor Vaccines DNA medicine Animals Humans Molecular Biology Mice Inbred BALB C Chemokine CCL21 Immunogenicity Mammary Neoplasms Experimental Molecular biology Tumor antigen Disease Models Animal biology.protein Molecular Medicine Female Adjuvant CCL21 |
Zdroj: | Cancer Gene Therapy. 19:69-76 |
ISSN: | 1476-5500 0929-1903 |
Popis: | 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. |
Databáze: | OpenAIRE |
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