Novel metronomic chemotherapy and cancer vaccine combinatorial strategy for hepatocellular carcinoma in a mouse model

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• 作者：Maria Tagliamonte ; Annacarmen Petrizzo…
• 关键词：PIVAC 14 ; Liver cancer ; Immunotherapy ; Cancer vaccine ; Metronomic chemotherapy ; Combinatorial strategy
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：64
• 期：10
• 页码：1305-1314
• 全文大小：553 KB
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• 作者单位：Maria Tagliamonte (1)
  Annacarmen Petrizzo (1)
  Maria Napolitano (2)
  Antonio Luciano (3)
  Claudio Arra (3)
  Piera Maiolino (4)
  Francesco Izzo (5)
  Maria Lina Tornesello (1)
  Luigi Aurisicchio (6)
  Gennaro Ciliberto (7)
  Franco M. Buonaguro (1)
  Luigi Buonaguro (1)
  
  1. Laboratory of Molecular Biology and Viral Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione Pascale-- IRCCS, Naples, Italy
  2. Laboratory of Clinical Immunology, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione Pascale-- IRCCS, Naples, Italy
  3. Animal Facility, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione Pascale-- IRCCS, Naples, Italy
  4. Pharmacy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione Pascale-- IRCCS, Naples, Italy
  5. Hepato-Biliary Surgery Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione Pascale-- IRCCS, Naples, Italy
  6. Takis, S.r.l., Rome, Italy
  7. Scientific Direction, Istituto Nazionale per lo Studio e la Cura dei Tumori, “Fondazione Pascale-- IRCCS, Naples, Italy
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851

文摘

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- %. 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. Keywords PIVAC 14 Liver cancer Immunotherapy Cancer vaccine Metronomic chemotherapy Combinatorial strategy