Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Postbox 9101, 6500 HB Nijmegen, The Netherlands.
Semin Immunol. 2011 Feb;23(1):12-20. doi: 10.1016/j.smim.2011.01.001. Epub 2011 Jan 26.
During the past decade, the immunotherapeutic potential of ex vivo generated professional antigen presenting dendritic cells (DCs) has been explored in the clinic. Albeit safe, clinical results have thus far been limited. A major disadvantage of current cell-based dendritic cell (DC) therapies, preventing universal implementation of this form of immunotherapy, is the requirement that vaccines need to be tailor made for each individual. Targeted delivery of antigens to DC surface receptors in vivo would circumvent this laborious and expensive ex vivo culturing steps involved with these cell-based therapies. In addition, the opportunity to target natural and often rare DC subsets in vivo might have advantages over loading more artificial ex vivo cultured DCs. Preclinical studies show targeting antigens to DCs effectively induces humoral responses, while cellular responses are induced provided a DC maturation or activation stimulus is co-administered. Here, we discuss strategies to target antigens to distinct DC subsets and to simultaneously employ adjuvants to activate these cells to induce immunity.
在过去的十年中,人们已经在临床上探索了体外生成的专业抗原呈递树突状细胞(DC)的免疫治疗潜力。尽管安全,但迄今为止临床结果有限。目前基于细胞的树突状细胞(DC)疗法的一个主要缺点是,需要为每个个体定制疫苗,这阻碍了这种免疫疗法的普遍实施。体内将抗原靶向递送至 DC 表面受体将避免这些基于细胞的疗法所涉及的繁琐和昂贵的体外培养步骤。此外,与加载更多人工体外培养的 DC 相比,靶向体内天然且通常罕见的 DC 亚群具有优势。临床前研究表明,将抗原靶向 DC 可有效诱导体液反应,而在给予 DC 成熟或激活刺激物的情况下会诱导细胞反应。在这里,我们讨论了将抗原靶向不同 DC 亚群的策略,并同时使用佐剂来激活这些细胞以诱导免疫。