Advanced search
Start date

Association of the immunotherapy mediated by p19Arf and Interferon-beta gene transfer with immunogenic cell death induced by the chemotherapic doxorubicin for the treatment of cancer

Grant number: 13/09474-5
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2013
Effective date (End): January 31, 2018
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Bryan Eric Strauss
Grantee:Ruan Felipe Vieira Medrano
Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated scholarship(s):15/14804-0 - Development, Validation and Optimization of Combinatorial Cancer Immunotherapy Using Personalized Neoantigen Vaccines Together with Monoclonal Antibodies Targeting Immune Checkpoints, BE.EP.DR


The immune system may combat and prevent the development of tumor cells. However, during the many stages of tumorigenesis, tumor cells progressively lose their immunogenicity and become less susceptible to anti-tumor immune mechanisms. Furthermore, the immunosuppressive tumor environment can reverse these mechanisms and make this system work in favor of tumor cells. Thus, the restoration of the immune system can be considered as a determining factor for the success of cancer treatment. Among the methods that can be used for this purpose, the combination of cancer immunotherapy with chemotherapy can be considered as an interesting strategy. Because, at the same time, such association can activate an immune response, reduce the immunosuppressive mechanisms and enhance the susceptibility of tumor cells to immune attack. Data from our laboratory also show a synergistic effect between these therapies. First, we have demonstrated that the gene transfer of p19Arf (tumor suppressor protein) and Interferon-beta (IFN², immunomodulatory cytokine) mediated by adenovirus induces cell death and an antitumor immune response against a secondary challenge. Then, the combination of these vectors was used as immunotherapy prior to treatment with the chemotherapeutic agent cisplatin, resulting in a dramatic reduction of tumor progression compared to the individual therapies. Although this favorable response in the presence of both therapies, cisplatin does not induce immunogenic cell death (a strong immune antitumor activity mediated by dendritic cells and CD4 + and CD8 + cells). Thus, with the purpose of enhancing the antitumor immune response, it iwould interesting to associate the immunotherapy mediated by the gene transfer of p19Arf/IFN² with the immunogenic cell death induced by chemotherapeutic doxorubicin. We hypothesize that the immunostimulatory effects of the immunotherapy p19Arf/IFN² and the immunogenic cell death acts synergistically on the immune system, modulate the immunosuppression caused by the tumor microenvironment and favor the treatment of cancer.

News published in Agência FAPESP Newsletter about the scholarship:
Articles published in other media outlets (0 total):
More itemsLess items

Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DAVID, TAYNAH I. P.; CERQUEIRA, OTTO L. D.; LANA, MARLOUS G.; MEDRANO, V, RUAN F.; HUNGER, ALINE; STRAUSS, BRYAN E.. Response of human melanoma cell lines to interferon-beta gene transfer mediated by a modified adenoviral vector. SCIENTIFIC REPORTS, v. 10, n. 1, . (17/23068-0, 10/15025-0, 12/05066-7, 11/10656-5, 15/26580-9, 13/09474-5)
STRAUSS, BRYAN E.; OLIVEIRA SILVA, GISSELE ROLEMBERG; VIEIRA, IGOR DE LUNA; DUTRA CERQUEIRA, OTTO LUIZ; DEL VALLE, PAULO ROBERTO; VIEIRA MEDRANO, RUAN FELIPE; MENDONCA, SAMIR ANDRADE. Perspectives for cancer immunotherapy mediated by p19Arf plus interferon-beta gene transfer. Clinics, v. 73, n. 1, . (12/05066-7, 16/18197-3, 13/09474-5, 13/25167-5, 13/16074-3, 15/26580-9)
MEDRANO, RUAN F. V.; HUNGER, ALINE; MENDONCA, SAMIR ANDRADE; BARBUTO, JOSE ALEXANDRE M.; STRAUSS, BRYAN E.. Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy. ONCOTARGET, v. 8, n. 41, p. 71249-71284, . (11/10656-5, 15/26580-9, 13/09474-5, 13/25167-5)
HUNGER, ALINE; MEDRANO, V, RUAN F.; ZANATTA, DANIELA B.; DEL VALLE, PAULO R.; MERKEL, CHRISTIAN A.; SALLES, THIAGO DE ALMEIDA; FERRARI, DANIEL G.; FURUYA, TATIANE K.; BUSTOS, SILVINA O.; SAITO, RENATA DE FREITAS; et al. Reestablishment of p53/Arf and interferon-beta pathways mediated by a novel adenoviral vector potentiates antiviral response and immunogenic cell death. CELL DEATH DISCOVERY, v. 3, . (11/10656-5, 13/09474-5, 13/25167-5)
VIEIRA MEDRANO, RUAN FELIPE; PORTELA CATANI, JOAO PAULO; RIBEIRO, ALINE HUNGER; TOMAZ, SAMANTA LOPES; MERKEL, CHRISTIAN A.; COSTANZI-STRAUSS, EUGENIA; STRAUSS, BRYAN E.. Vaccination using melanoma cells treated with p19arf and interferon beta gene transfer in a mouse model: a novel combination for cancer immunotherapy. CANCER IMMUNOLOGY IMMUNOTHERAPY, v. 65, n. 4, p. 371-382, . (11/10656-5, 13/09474-5, 14/11524-3, 13/25167-5)
PORTELA CATANI, JOAO PAULO; MEDRANO, RUAN F. V.; HUNGER, ALINE; DEL VALLE, PAULO; ADJEMIAN, SANDY; ZANATTA, DANIELA BERTOLINI; KROEMER, GUIDO; COSTANZI-STRAUSS, EUGENIA; STRAUSS, BRYAN E.. Intratumoral Immunization by p19Arf and Interferon-beta Gene Transfer in a Heterotopic Mouse Model of Lung Carcinoma. TRANSLATIONAL ONCOLOGY, v. 9, n. 6, p. 565-574, . (11/10656-5, 12/25380-8, 13/09474-5, 14/11524-3, 13/25167-5)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MEDRANO, Ruan Felipe Vieira. Remediation of the p53/Arf and Interferon-beta pathways as a cancer immunotherapy strategy: a gene transfer approach. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

Please report errors in scientific publications list by writing to: