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Rational combination between checkpoint blockade and gene therapy with p19Arf and IFN-beta in a mouse model of melanoma

Grant number: 18/25555-9
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): April 01, 2019
Effective date (End): August 31, 2024
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Bryan Eric Strauss
Grantee:Ana Carolina Martins Domingues
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
Associated scholarship(s):22/04368-1 - Rational combination of checkpoint blockade and gene therapy with p14Arf and IFN-b in patient-derived organotypic tumor spheroids, BE.EP.DD


The immune system functions include regulation by immune checkpoints (ICPs) - pathways that either inhibit or activate the immune cells, mainly T lymphocytes. Cancer cells and Antigen Presenting Cells (APCs) found in the tumor microenvironment can express ICPs with different patterns, thus diminishing the immune response to the disease. Blocking the cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and the programmed death 1 (PD-1) and its ligand (PD-L1) ICPs have revolutionized cancer treatment, especially for Melanoma. But when used as monotherapies or combined with each other, these ICP inhibitors do not show efficacy for all patients and can trigger side effects. Therefore, the search for new immunotherapy strategies is needed. Our group has been developing an immunotherapy involving the gene transfer of p19Arf and interferon-² (IFN-²) and we seek to potentiate its affect by associating it with checkpoint blockade. In this study, we will evaluate potentially dysregulated ICPs after treating murine Melanoma with p19Arf and IFN² gene therapy in order to then apply a rational combination of checkpoint blockade with our gene therapy approach. (AU)

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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)

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