Arce Frederick, Breckpot Karine, Collins Mary, Escors David
Division of Infection and Immunity, Medical School of the Royal Free and University College London, 46 Cleveland Street, London W1T 4JF, United Kingdom.
Curr Cancer Ther Rev. 2011 Nov;7(4):248-260. doi: 10.2174/157339411797642605.
Delivery of tumour-associated antigens (TAA) in a way that induces effective, specific immunity is a challenge in anti-cancer vaccine design. Circumventing tumour-induced tolerogenic mechanisms in vivo is also critical for effective immunotherapy. Effective immune responses are induced by professional antigen presenting cells, in particular dendritic cells (DC). This requires presentation of the antigen to both CD4(+) and CD8(+) T cells in the context of strong co-stimulatory signals. Lentiviral vectors have been tested as vehicles, for both ex vivo and in vivo delivery of TAA and/or activation signals to DC, and have been demonstrated to induce potent T cell mediated immune responses that can control tumour growth. This review will focus on the use of lentiviral vectors for in vivo gene delivery to DC, introducing strategies to target DC, either targeting cell entry or gene expression to improve safety of the lentiviral vaccine or targeting dendritic cell activation pathways to enhance performance of the lentiviral vaccine. In conclusion, this review highlights the potential of lentiviral vectors as a generally applicable 'off-the-shelf' anti-cancer immunotherapeutic.
以诱导有效、特异性免疫的方式递送肿瘤相关抗原（TAA）是抗癌疫苗设计中的一项挑战。在体内规避肿瘤诱导的耐受机制对于有效的免疫治疗也至关重要。有效的免疫反应是由专业的抗原呈递细胞，特别是树突状细胞（DC）诱导的。这需要在强烈的共刺激信号背景下将抗原呈递给CD4(+)和CD8(+) T细胞。慢病毒载体已被测试作为将TAA和/或激活信号体外和体内递送至DC的载体，并已被证明可诱导有效的T细胞介导的免疫反应，从而控制肿瘤生长。本综述将聚焦于慢病毒载体用于体内基因递送至DC，介绍靶向DC的策略，即要么靶向细胞进入或基因表达以提高慢病毒疫苗的安全性，要么靶向树突状细胞激活途径以增强慢病毒疫苗的性能。总之，本综述强调了慢病毒载体作为一种普遍适用的“现成”抗癌免疫疗法的潜力。
