Centre of Excellence for Biomedical Research; University of Genoa; Genoa, Italy; Department of Internal Medicine; University of Genoa; Genoa, Italy.
Centre of Excellence for Biomedical Research; University of Genoa; Genoa, Italy; Department of Surgical Sciences; University of Genoa; Genoa, Italy.
Hum Vaccin Immunother. 2013 Dec;9(12):2543-7. doi: 10.4161/hv.26147. Epub 2013 Aug 26.
Cancer vaccines represent a promising therapeutic approach for which prime time is imminent. However, clinical efficacy must be improved in order for cancer vaccines to become a valid alternative or complement to traditional cancer treatments. Considerable efforts have been undertaken so far to better understand the fundamental requirements for clinically-effective cancer vaccines. Recent data emphasize that important requirements, among others, are (1) the use of multi-epitope immunogens, possibly deriving from different tumor antigens; (2) the selection of effective adjuvants; (3) the association of cancer vaccines with agents able to counteract the regulatory milieu present in the tumor microenvironment; and (4) the need to choose the definitive formulation and regimen of a vaccine after accurate preliminary tests comparing different antigen formulations. The first requirement deals with issues related to HLA restriction of tumor antigen presentation, as well as usefulness of tumor antigen spreading and counteraction of immune escape phenomena, linked to tumor antigen down-modulation, for an effective anti-cancer immune response. The second point underscores the necessity of optimal activation of innate immunity to achieve an efficient adaptive anti-cancer immune response. The third point focuses on the importance to inhibit subsets of regulatory cells. The last requirement stresses the concept that the regimen and formulation of the vaccine impacts profoundly on cancer vaccine efficacy. A new generation of cancer vaccines, provided with both immunological and clinical efficacy, will hopefully soon address these requirements.
癌症疫苗代表了一种很有前途的治疗方法，其黄金时期即将到来。然而，为了使癌症疫苗成为传统癌症治疗的有效替代或补充，其临床疗效必须得到提高。到目前为止，已经做出了相当大的努力来更好地了解临床有效癌症疫苗的基本要求。最近的数据强调，重要的要求包括：(1) 使用多表位免疫原，可能来自不同的肿瘤抗原；(2) 选择有效的佐剂；(3) 将癌症疫苗与能够对抗肿瘤微环境中存在的调节环境的药物联合使用；以及 (4) 在对不同抗原制剂进行准确的初步测试后，需要选择疫苗的最终制剂和方案。第一个要求涉及与 HLA 限制肿瘤抗原呈递以及肿瘤抗原扩散和对抗免疫逃逸现象相关的问题，这些现象与肿瘤抗原下调有关，对于有效的抗肿瘤免疫反应是必要的。第二个要点强调了最佳激活先天免疫以实现有效的适应性抗肿瘤免疫反应的必要性。第三个要点侧重于抑制调节性细胞亚群的重要性。最后一个要求强调了疫苗的方案和制剂对癌症疫苗疗效有深远影响的概念。新一代的癌症疫苗，如果具有免疫和临床疗效，有望很快满足这些要求。
