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Investigation of antitumor immune response mechanisms induced by combining p19Arf and IFN beta gene transfer

Grant number: 14/11524-3
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): February 01, 2015
Effective date (End): November 30, 2015
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Bryan Eric Strauss
Grantee:João Paulo Portela Catani
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


Between 1979-1980, several laboratories identified and characterized viral genes, whose products would be sufficient to immortalize and transform mammal cell lines, which led to a simplistic vision in which cancer would be a genetic disease, conferring cellular autonomy. In the beginning of the XXI century, the idea that cancer was a more complex pathology became completely accepted. Despite of the actual scientific knowledge on the mechanisms that enable tumor genesis and progression, the actual clinical methods are still derived from the initial idea that cancer is a simple proliferative disease. In this context, emerge the need to develop new therapies, which synergize with the actual ones and aim to destabilize other mechanisms, beyond proliferation. Among the possible targets for new therapies, the capacity of the tumor to evade the immune system is now considered. Our group developed with success, adenoviral vectors which aim at restoring p53 pathway, as well as antitumor immunostimulation with interferon beta (IFN²). In a murine model of lung carcinoma (Lewis Lung Carcinoma - LLC1), we observed that p19Arf gene transfer was sufficient for the induction of cell death in vitro. Intratumoral injection of adenoviral vectors carrying p19Arf or/and IFN², shows that IFN² has a major role in the reduction of tumor growth. Gene transfer of both p19Arf and IFN² did not show inhibition of primary tumor growth. Nonetheless, when treated mice were subjected to a rechallenge, gene transfer of both p19Arf and IFN² had a significant effect in immunoprotection. This effect was also observed in another experiment, when mice were vaccinated with LLC1 cells transduced ex vivo. These results suggest that p19Arf and IFN² combination induces a specific immune response. We hope that through analysis from microarray, and immune cell infiltration of tumors, we can validate these observations. (AU)

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Scientific publications (4)
(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)
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)
MEDRANO, RUAN F., V; SALLES, THIAGO A.; DARIOLLI, RAFAEL; ANTUNES, FERNANDA; FEITOSA, VALKER A.; HUNGER, ALINE; CATANI, JOAO P. P.; MENDONCA, SAMIR A.; TAMURA, RODRIGO E.; LANA, MARLOUS G.; et al. Potentiation of combined p19Arf and interferon-beta cancer gene therapy through its association with doxorubicin chemotherapy. SCIENTIFIC REPORTS, v. 12, n. 1, p. 14-pg., . (18/04800-5, 13/09474-5, 15/26580-9, 11/10656-5, 11/21256-8, 14/11524-3, 12/05066-7)
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)
PORTELA CATANI, JOAO PAULO; RIECHELMANN, RACHEL P.; ADJEMIAN, SANDY; STRAUSS, BRYAN E.. Near future of tumor immunology: Anticipating resistance mechanisms to immunotherapies, a big challenge for clinical trials. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 13, n. 5, p. 3-pg., . (14/11524-3, 12/25380-8, 13/25167-5)

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