title: Oncolytic Adenovirus Loaded with L-carnosine as Novel Strategy to Enhance the Antitumor Activity.
abstract: Oncolytic viruses are able to specifically replicate, infect, and kill only cancer cells. Their combination with chemotherapeutic drugs has shown promising results due to the synergistic action of virus and drugs; the combinatorial therapy is considered a potential clinically relevant approach for cancer. In this study, we optimized a strategy to absorb peptides on the viral capsid, based on electrostatic interaction, and used this strategy to deliver an active antitumor drug. We used L-carnosine, a naturally occurring histidine dipeptide with a significant antiproliferative activity. An ad hoc modified, positively charged L-carnosine was combined with the capsid of an oncolytic adenovirus to generate an electrostatic virus-carnosine complex. This complex showed enhanced antitumor efficacy in vitro and in vivo in different tumor models. In HCT-116 colorectal and A549 lung cancer cell lines, the complex showed higher transduction ratio and infectious titer compared with an uncoated oncolytic adenovirus. The in vivo efficacy of the complex was tested in lung and colon cancer xenograft models, showing a significant reduction in tumor growth. Importantly, we investigated the molecular mechanisms underlying the effects of complex on tumor growth reduction. We found that complex induces apoptosis in both cell lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in future studies also for delivery of other bioactive drugs. Mol Cancer Ther; 15(4); 651-60. ©2016 AACR.
authors: Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, Italy.
authors: Mariangela
authors: M
authors: Garofalo
authors: Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, Italy.
authors: Barbara
authors: B
authors: Iovine
authors: Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. Oncos Therapeutics Ltd., Helsinki, Finland. Department of Virology, National Institute of Public Health-National Institute of Hygiene, Warsaw, Poland.
authors: Lukasz
authors: L
authors: Kuryk
authors: Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors: Cristian
authors: C
authors: Capasso
authors: Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
authors: Mari
authors: M
authors: Hirvinen
authors: Department of Movement Sciences and Wellness (DiSMEB), University of Naples Parthenope and CEINGE-Biotecnologie Avanzate, Naples, Italy.
authors: Andrea
authors: A
authors: Vitale
authors: Division of Pharmaceutical Biosciences and Centre for Drug Research, University of Helsinki, Helsinki, Finland.
authors: Marjo
authors: M
authors: Yliperttula
authors: Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, Italy.
authors: Maria Assunta
authors: MA
authors: Bevilacqua
authors: Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. vincenzo.cerullo@helsinki.fi.
authors: Vincenzo
authors: V
authors: Cerullo
mesh_terms: D000256:Adenoviridae / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002336:Carnosine / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000737:chemistry / Q000235:genetics*; D014161:Transduction, Genetic; D047368:Tumor Burden; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D055551:HSP27 Heat-Shock Proteins; D016209:Interleukin-8; D002336:Carnosine