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Assessment of p14Arf and IFN-beta gene transfer in human primary melanoma for ex vivo evidence of immunological response and in vivo therapeutic efficacy

Grant number: 17/23068-0
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): December 01, 2017
Effective date (End): April 30, 2022
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Bryan Eric Strauss
Grantee:Otto Luiz Dutra Cerqueira
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 research grant:15/26580-9 - Cancer gene therapy: strategic positioning for translational studies, AP.TEM


With this sub-project (described in the main proposal as Project 8), we intend to carry out essential tests that demonstrate that melanoma cells derived from patients respond to treatment with adenoviral vector bearing p14Arf and IFN-beta (interferon-beta). Here, we will explore the induction of cell death, the mechanism of cell death, the potential for activation of the immune system and inhibition of tumor progression in vivo. Since the immune response can not be evaluated in vivo, we will use ex vivo models for this purpose, where tumor cells will be treated with the vector, exposed to human dendritic cells (DC) and evaluated with respect to the presence of activation markers. Then, human T cells will be activated through their co-culture with the DCs. The activation state of T cells will be assessed by immunophenotyping and functional assays. In parallel, the primary human melanoma cells will be implanted s.c. of immunodeficient mice and, after tumor formation, treated with gene therapy in situ using adenovirus encoding p14Arf and IFN-Beta. We hope to reveal the reduction of tumor progression due to the induction of cell death, but this model will not reveal aspects of the immune response.

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Scientific publications
(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)
TESSAROLLO, NAYARA GUSMAO; DOMINGUES, ANA CAROLINA M.; ANTUNES, FERNANDA; DOS SANTOS DA LUZ, JEAN CARLOS; RODRIGUES, OTAVIO AUGUSTO; DUTRA CERQUEIRA, OTTO LUIZ; STRAUSS, BRYAN E.. Nonreplicating Adenoviral Vectors: Improving Tropism and Delivery of Cancer Gene Therapy. CANCERS, v. 13, n. 8, . (17/25290-2, 17/23068-0, 17/25284-2, 18/25555-9)
CERQUEIRA, OTTO LUIZ DUTRA; CLAVIJO-SALOMON, MARIA ALEJANDRA; CARDOSO, ELAINE CRISTINA; CITRANGULO TORTELLI JUNIOR, THARCISIO; MENDONCA, SAMIR ANDRADE; BARBUTO, JOSE ALEXANDRE M.; STRAUSS, BRYAN E.. Combined p14ARF and Interferon-beta Gene Transfer to the Human Melanoma Cell Line SK-MEL-147 Promotes Oncolysis and Immune Activation. FRONTIERS IN IMMUNOLOGY, v. 11, . (17/13686-9, 17/23068-0, 15/26580-9)
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)

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