title: Novel metronomic chemotherapy and cancer vaccine combinatorial strategy for hepatocellular carcinoma in a mouse model.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology and Viral Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, "Fondazione Pascale" - IRCCS, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Tagliamonte
authors.forename: Annacarmen
authors.initials: A
authors.lastname: Petrizzo
authors.forename: Maria
authors.initials: M
authors.lastname: Napolitano
authors.forename: Antonio
authors.initials: A
authors.lastname: Luciano
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.forename: Piera
authors.initials: P
authors.lastname: Maiolino
authors.forename: Francesco
authors.initials: F
authors.lastname: Izzo
authors.forename: Maria Lina
authors.initials: ML
authors.lastname: Tornesello
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurisicchio
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: Franco M
authors.initials: FM
authors.lastname: Buonaguro
authors.forename: Luigi
authors.initials: L
authors.lastname: Buonaguro
mesh_terms: D059250:Administration, Metronomic; D000477:Alkylating Agents / Q000627:therapeutic use; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006509:Hepatitis B / Q000150:complications / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000378:metabolism; D008113:Liver Neoplasms / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D008297:Male; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D043823:Taxoids / Q000627:therapeutic use; D019098:Telomerase / Q000276:immunology / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D000956:Antigens, Viral; D019496:Cancer Vaccines; D016056:Immunodominant Epitopes; D043823:Taxoids; D019098:Telomerase; C509187:Tert protein, mouse