Tagliamonte Maria, Petrizzo Annacarmen, Napolitano Maria, Luciano Antonio, Arra Claudio, Maiolino Piera, Izzo Francesco, Tornesello Maria Lina, Aurisicchio Luigi, Ciliberto Gennaro, Buonaguro Franco M, Buonaguro Luigi
Laboratory of Molecular Biology and Viral Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione Pascale" - IRCCS, Naples, Italy.
Cancer Immunol Immunother. 2015 Oct;64(10):1305-14. doi: 10.1007/s00262-015-1698-0. Epub 2015 May 6.
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and represents the third and the fifth leading cause of cancer-related death worldwide in men and women, respectively. Hepatitis B virus (HBV) and hepatitis C virus (HCV) chronic infections account for pathogenesis of more than 80 % of primary HCC. HCC prognosis greatly varies according to stage at beginning of treatment, but the overall 5-year survival rate is approximately 5-6 %. Given the limited number of effective therapeutic strategies available, immunotherapies and therapeutic cancer vaccines may help in improving the clinical outcome for HCC patients. However, the few clinical trials conducted to date have shown contrasting results, indicating the need for improvements. In the present study, a novel combinatorial strategy, based on metronomic chemotherapy plus vaccine, is evaluated in a mouse model. The chemotherapy is a multi-drug cocktail including taxanes and alkylating agents, which is administered in a metronomic-like fashion. The vaccine is a multi-peptide cocktail including HCV as well as universal tumor antigen TERT epitopes. The combinatorial strategy designed and evaluated in the present study induces an enhanced specific T cell response, when compared to vaccine alone, which correlates to a reduced Treg frequency. Such results are highly promising and may pave way to relevant improvements in immunotherapeutic strategies for HCC and beyond.
肝细胞癌（HCC）是最常见的原发性肝癌，分别是全球男性和女性癌症相关死亡的第三和第五大主要原因。乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）慢性感染占原发性HCC发病机制的80%以上。HCC的预后根据治疗开始时的阶段有很大差异，但总体5年生存率约为5-6%。鉴于可用的有效治疗策略数量有限，免疫疗法和治疗性癌症疫苗可能有助于改善HCC患者的临床结局。然而，迄今为止进行的少数临床试验显示出相互矛盾的结果，表明需要改进。在本研究中，在小鼠模型中评估了一种基于节拍化疗加疫苗的新型联合策略。化疗是一种多药鸡尾酒，包括紫杉烷和烷化剂，以类似节拍的方式给药。疫苗是一种多肽鸡尾酒，包括HCV以及通用肿瘤抗原TERT表位。与单独使用疫苗相比，本研究中设计和评估的联合策略诱导了增强的特异性T细胞反应，这与Treg频率降低相关。这些结果非常有前景，可能为HCC及其他疾病的免疫治疗策略的相关改进铺平道路。
