Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Campus Berlin-Buch and Campus Virchow-Klinikum, Berlin, Germany.
Cancer Gene Ther. 2012 Jan;19(1):69-76. doi: 10.1038/cgt.2011.69. Epub 2011 Oct 14.
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.
二级淋巴组织趋化因子（SLC/CCL21）是一种 CC 趋化因子，在各种淋巴组织中持续表达，与成熟树突状细胞（DC）和独特的 T 细胞和 B 细胞亚群上的趋化因子受体 CCR7 结合。在体内，CCL21 调节 DC 和 T 细胞之间的相互作用，因此是适应性免疫反应的关键调节剂。我们询问 CCL21 是否能够增强针对 Her2/neu 的基于 DNA 的疫苗在具有同源 Her2/neu+肿瘤细胞（D2F2/E2）的 Balb/c 小鼠模型中的免疫原性。小鼠在第 1 天肌肉内接种质粒 DNA（pDNA），第 15 天加强；第 25 天皮下进行肿瘤挑战。CCL21 和 Her-2/neu 的共表达导致诱导 TH1 极化免疫反应，并显著改善 DNA 疫苗的保护作用。共表达肿瘤抗原 pDNA（Her2/neu）与 pDNA（GM-CSF）和 pDNA（CCL21）作为佐剂可进一步提高疫苗的保护作用（第 35 天无肿瘤小鼠的比例为 70%，而单独使用任一佐剂的比例为 40%，单独使用肿瘤抗原的比例为 5-10%）。我们的结果表明，CCL21 是 DNA 疫苗接种的有效佐剂，特别是与粒细胞-巨噬细胞集落刺激因子（GM-CSF）联合使用时。在 Her2/neu+乳腺癌的最小残留疾病中，使用 pDNA（Her2/neu/CCL21/GM-CSF）疫苗的临床应用可能特别有前途。
