Koski Gary K, Cohen Peter A, Roses Robert E, Xu Shuwen, Czerniecki Brian J
Department of Immunology, Center for Surgery Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Immunol Rev. 2008 Apr;222:256-76. doi: 10.1111/j.1600-065X.2008.00617.x.
Despite initial enthusiasm, dendritic cell (DC)-based anti-cancer vaccines have yet to live up to their promise as one of the best hopes for generating effective anti-tumor immunity. One of the principal reasons for the generally disappointing results achieved thus far could be that the full potential of DCs has not been effectively exploited. Here, we argue that dramatic improvements in vaccine efficacy will probably require a careful re-evaluation of current vaccine design. The formulation of new strategies must take into account the natural history of DCs, particularly their role in helping the immune system deal with infection. Equally critical is the emerging importance of soluble factors, notably interleukin-12, in modulating the quality of immune responses. Vaccines should also be designed to recruit helper T cells and antibody-producing B cells rather than simply cytotoxic T lymphocytes. Finally, the judicious selection of tumor, target antigen, and disease stage best suited for treatment should serve as the foundation of trial designs. Our discussion addresses a recent clinical vaccine trial to treat early breast cancer, where many elements of this new strategy were put into practice.
尽管最初人们热情高涨，但基于树突状细胞（DC）的抗癌疫苗尚未兑现其作为产生有效抗肿瘤免疫的最大希望之一的承诺。迄今为止取得的结果普遍令人失望的主要原因之一可能是DC的全部潜力尚未得到有效利用。在此，我们认为疫苗效力的显著提高可能需要对当前疫苗设计进行仔细的重新评估。新策略的制定必须考虑DC的自然历程，尤其是它们在帮助免疫系统应对感染方面的作用。同样关键的是可溶性因子（尤其是白细胞介素-12）在调节免疫反应质量方面日益重要的作用。疫苗还应设计为招募辅助性T细胞和产生抗体的B细胞，而不仅仅是细胞毒性T淋巴细胞。最后，明智地选择最适合治疗的肿瘤、靶抗原和疾病阶段应作为试验设计的基础。我们的讨论涉及一项治疗早期乳腺癌的近期临床疫苗试验，该试验将这一新策略的许多要素付诸实践。
