Rueda Felix, Eich Christina, Cordobilla Begoña, Domingo Pere, Acosta Gerardo, Albericio Fernando, Cruz Luis J, Domingo Joan C
Department of Biochemistry and Molecular Biology, University of Barcelona, Diagonal 643, 08028 Barcelona, Spain.
Department of Cell Biology Erasmus Medical Center Rotterdam, The Netherlands.
Immunobiology. 2017 Nov;222(11):989-997. doi: 10.1016/j.imbio.2017.06.002. Epub 2017 Jun 10.
Nanoliposomes (NLs) hold promise as new highly specific nanomedicine for anti-tumor vaccines, since they could be targeted to specific receptors on dendritic cell (DC) to induce maturation and activation and increase the anti-tumor immune response. Here we studied a NLs formulation targeted or not to FcR (the receptor for the IgG Fc fragment) for the treatment of androgen-responsive prostate cancer. Luteinizing-hormone-releasing hormone (LHRH) peptide (B- and T-cell epitopes), in tandem with a tetanus toxoid T-helper epitope (830-844 region) and several TLR (Toll-Like Receptor) ligands as adjuvants were co-encapsulated. Specific uptake in vitro of LHRH-TT liposomes targeted to the FcRs of human DCs was enhanced. DC maturation/activation, cytokine production and lymphocyte activation were consistently higher in targeted than non-targeted liposomes. Similar increase was observed as more adjuvants were administrated. Targeting to specific receptor and co-encapsulation of several TLR adjuvants are essential factors for the immune response in peptide based liposome vaccine.
纳米脂质体（NLs）有望成为新型高度特异性的抗肿瘤疫苗纳米药物，因为它们可以靶向树突状细胞（DC）上的特定受体，诱导其成熟和激活，并增强抗肿瘤免疫反应。在此，我们研究了一种靶向或不靶向FcR（IgG Fc片段受体）的纳米脂质体制剂，用于治疗雄激素反应性前列腺癌。黄体生成素释放激素（LHRH）肽（B细胞和T细胞表位）与破伤风类毒素T辅助表位（830-844区域）以及几种TLR（Toll样受体）配体作为佐剂共同包封。靶向人DCs的FcR的LHRH-TT脂质体在体外的特异性摄取增强。靶向脂质体组的DC成熟/激活、细胞因子产生和淋巴细胞激活始终高于非靶向脂质体组。随着使用更多佐剂，也观察到了类似的增加。靶向特定受体以及共同包封几种TLR佐剂是基于肽的脂质体疫苗免疫反应的关键因素。
