Rinaldi M, Iurescia S, Fioretti D, Ponzetto A, Carloni G
Int J Immunopathol Pharmacol. 2009 Apr-Jun;22(2):269-77. doi: 10.1177/039463200902200203.
Current therapies against hepatocellular carcinoma (HCC) are not curative in the majority of patients. In the past, immunotherapy approaches aimed to non-specifically stimulate immune response were quite ineffective. New treatments based on stimulation of specific anti-tumor immune response are currently proposed and appear more promising. Tumor-specific antigens identified in HCC demonstrated immunogenicity both in preclinical and clinical trials. Effectiveness in animal studies raised interest in the clinical applicability of non-specific adoptive immunotherapy that prevented disease recurrence after tumor resection. Dendritic cell (DC)-based tumor vaccines achieved encouraging results, and cellular vaccines based on DCs have already entered clinical trials. Preventive and therapeutic DNA vaccination have been proposed, all based on tumor-associated antigens (TAAs), either modified or not, an example being alpha-fetoprotein (AFP). The concomitant expression of co-stimulatory molecules and cytokines was used to increase tumor immunogenicity. Syngeneic or nude mice models indicated that immunotherapy for HCC could stimulate an anti-tumor T-cell response leading to clinical benefit devoid of significant toxicity. The use of DNA-based vaccination raises exciting possibilities in preventing HCC in high-risk individuals such as those with cirrhosis. Novel immunotherapy strategies may contribute in the future to prevention and treatment of HCC.
目前针对肝细胞癌（HCC）的治疗方法在大多数患者中并不能治愈。过去，旨在非特异性刺激免疫反应的免疫治疗方法效果不佳。目前提出了基于刺激特异性抗肿瘤免疫反应的新治疗方法，且似乎更具前景。在HCC中鉴定出的肿瘤特异性抗原在临床前和临床试验中均显示出免疫原性。动物研究中的有效性引发了人们对非特异性过继性免疫治疗临床适用性的兴趣，这种治疗可预防肿瘤切除后疾病复发。基于树突状细胞（DC）的肿瘤疫苗取得了令人鼓舞的结果，基于DC的细胞疫苗已进入临床试验。已提出预防性和治疗性DNA疫苗接种，均基于肿瘤相关抗原（TAA），无论是否经过修饰，例如甲胎蛋白（AFP）。共刺激分子和细胞因子的共表达用于增强肿瘤免疫原性。同基因或裸鼠模型表明，HCC免疫治疗可刺激抗肿瘤T细胞反应，从而带来临床益处且无明显毒性。基于DNA的疫苗接种在预防高危个体（如肝硬化患者）的HCC方面带来了令人兴奋的可能性。新型免疫治疗策略未来可能有助于HCC的预防和治疗。
