659. Oncolytic Adenovirus Loaded with Bioactive Modified Peptide as a Novel Approach to Treat Cancer
| Autor: | Mariangela Garofalo, Maria Assunta Bevilacqua, Barbara Iovine, Marjo Yliperttula, Lukasz Kuryk, Vincenzo Cerullo, Cristian Capasso, Mari Hirvinen, Andrea Vitale |
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| Rok vydání: | 2016 |
| Předmět: |
Pharmacology
Oncolytic adenovirus 0303 health sciences Colorectal cancer medicine.medical_treatment Cancer Biology medicine.disease 3. Good health Oncolytic virus Radiation therapy 03 medical and health sciences 0302 clinical medicine Viral replication 030220 oncology & carcinogenesis Drug Discovery Immunology Cancer cell Genetics medicine Cancer research Molecular Medicine Lung cancer Molecular Biology 030304 developmental biology |
| Zdroj: | Molecular Therapy. 24:S261 |
| ISSN: | 1525-0016 |
| Popis: | Cancer is still a leading cause of death worldwide. Although many kinds of treatment have been developed during the past decades, there is still a lack of effective therapy for advanced cancer. Currently treatments such as surgery, chemotherapy and radiotherapy can help to improve patient prognosis and increase patient life expectancy. Therefore new treatment strategies against cancer are in high demand. Efficient anticancer agent and its targeted delivery into the tumor mass is a key prerequisite for the successful cancer therapy. Oncolytic virotherapy is emerging as a potential approach to treat cancer, using viruses, which are specifically engineered to selectively infect, replicate in and kill cancer cells without causing damage to normal cells. Their combination with chemotherapeutic agents have shown promising results due to the synergistic effect of viruses and drugs; therefore the combinatorial therapy is considered a beneficial approach for cancer treatment. Taken into account these considerations we optimized a strategy to conjugate peptides on the viral capsid, based on electrostatic interaction and used this strategy to deliver an active anti-tumor dipeptide. We used L-carnosine, a naturally occurring histidine dipeptide with anti-proliferative activity. A modified L-carnosine, positively charged was absorbed onto the viral capsid of an oncolytic adenovirus to generate a virus-carnosine complex. The complex showed enhanced anti tumor efficacy in vitro and in vivo and higher infectious titer compared to a naked oncolytic adenovirus in colorectal and lung cancer cells. The in vivo efficacy of the complex was analyzed in lung and colon cancer xenograft models, displaying a significant reduction in tumor growth and synergistic effect between virus and dipeptide. Moreover, we studied the molecular mechanisms underlying the effects of complex on tumor growth reduction. Complex can induce apoptosis in both cells lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in further studies also for specific delivery of other active drugs. |
| Databáze: | OpenAIRE |
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