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Cancer gene therapy: strategic positioning for translational studies

Grant number: 15/26580-9
Support type:Research Projects - Thematic Grants
Duration: May 01, 2017 - April 30, 2023
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Bryan Eric Strauss
Grantee:Bryan Eric Strauss
Home 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
Assoc. researchers:Eugenia Costanzi-Strauss ; Gilberto de Castro Junior ; Jose Alexandre Marzagão Barbuto ; Maria Lucia Zaidan Dagli ; Rodrigo Ramella Munhoz
Associated scholarship(s):19/03055-7 - Induction of immunogenic cell death by associating gene transfer and chemotherapy in human prostate carcinoma cells, BP.DD
19/08147-7 - Analysis of the metabolic profile and mathematical modeling of cisplatin-induced chemoresistant A549 NSCLC cells through Jardi1b overexpression, BE.PQ
18/25555-9 - Rational combination between checkpoint blockade and gene therapy with p19Arf and IFN-beta in a mouse model of melanoma, BP.DD
+ associated scholarships 17/25290-2 - A study of the role of neoantigens in the modulation of the anti-tumor response promoted by the treatment of B16 cells with p19Arf and IFN-beta., BP.PD
18/04800-5 - The role of p73 isoforms in the response of B16F10 cells to transduction with adenoviral vectors carrying p19Arf and IFNbeta cDNAs., BP.PD
17/25284-2 - Construction and characterization of adenoviral vectors encoding the canine cDNAs for p14Arf and IFN-beta, BP.DD
17/23068-0 - Assessment of p14Arf and IFN-beta gene transfer in human primary melanoma for ex vivo evidence of immunological response and in vivo therapeutic efficacy, BP.PD - associated scholarships

Abstract

The burden of cancer on patient care and public health systems continues to grow, in part due to the aging population. Effective treatment for cancer is often not available, though new and improved approaches are being developed. Gene therapy has been in clinical use for over 25 years and its use for the treatment of cancer has shown several successes, including recent approval by the FDA for one such modality. Cancer gene therapy efforts in Brazil are well underway, but will require considerable investment in research and infrastructure in order to reach clinical application. The Viral Vector Laboratory (VVL, ICESP, FMUSP) has developed an immunotherapy for melanoma based on adenoviral vectors encoding p19Arf and interferon-beta, while the Gene Therapy Laboratory (GTL, ICB-USP) has developed a gene therapy approach for lung cancer involving adenoviral transfer of CDKN2a and p53. These adenovirus-mediated cancer gene therapy approaches have been shown to retard tumor progression, induce cell death and promote an important anti-tumor immune response when using in vitro and in vivo models. However promising, these approaches must pass through rigorous pre-clinical testing before application in patients can be considered. With this proposal, we aim to pave the way for such pre-clinical assays by implementing three strategies. First, production of adenovirus with adequate quantity and quality for in vivo assays with pre-clinical relevance will be established. Second, the mechanisms behind the cellular and immune responses after tumor treatment with the adenoviral vectors will be explored in mouse and human cell lines in tissue culture and in vivo. Third, clinically relevant animal models, including conditional mouse models and PDX (Patient Derived Xenografts), will be employed in order to show the merit of our approaches. This project will ensure that the VVL and GTL are positioned to cross the frontier between basic and clinical research in the near future. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications (11)
(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)
TORTELLI, JR., THARCISIO CITRANGULO; TAMURA, RODRIGO ESAKI; JUNQUEIRA, MARA DE SOUZA; MORORO, JANIO DA SILVA; BUSTOS, SILVINA ODETE; NATALINO, RENATO JOSE MENDONCA; RUSSELL, SHONAGH; DESAUBRY, LAURENT; STRAUSS, BRYAN ERIC; CHAMMAS, ROGER. Metformin-induced chemosensitization to cisplatin depends on P53 status and is inhibited by Jarid1b overexpression in non-small cell lung cancer cells. AGING-US, v. 13, n. 18, p. 21914-21940, SEP 30 2021. Web of Science Citations: 0.
DEL VALLE, PAULO ROBERTO; MENDONCA, SAMIR ANDRADE; ANTUNES, FERNANDA; HUNGER, ALINE; TAMURA, RODRIGO E.; ZANATTA, DANIELA BERTOLINI; STRAUSS, BRYAN E. Exploration of p53 plus interferon-beta gene transfer for the sensitization of human colorectal cancer cell lines to cell death. CANCER BIOLOGY & THERAPY, APR 2021. Web of Science Citations: 0.
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, OCT 22 2020. Web of Science Citations: 0.
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 OCT 21 2020. Web of Science Citations: 1.
CHICAYBAM, LEONARDO; BONAMINO, MARTIN H.; LUCKOW INVITTI, ADRIANA; BORTMAN ROZENCHAN, PATRICIA; DE LUNA VIEIRA, IGOR; STRAUSS, BRYAN E. Overhauling CAR T Cells to Improve Efficacy, Safety and Cost. CANCERS, v. 12, n. 9 SEP 2020. Web of Science Citations: 0.
DA-COSTA, R. C.; VIEIRA, I. L.; HUNGER, A.; TAMURA, R. E.; STRAUSS, B. E. p19Arf sensitizes B16 melanoma cells to interferon-beta delivered via mesenchymal stem cells in vitro. Brazilian Journal of Medical and Biological Research, v. 53, n. 3 2020. Web of Science Citations: 0.
VIEIRA, IGOR DE LUNA; TAMURA, RODRIGO ESAKI; HUNGER, ALINE; STRAUSS, BRYAN E. Distinct Roles of Direct Transduction Versus Exposure to the Tumor Secretome on Murine Endothelial Cells After Melanoma Gene Therapy with Interferon-beta and p19Arf. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, v. 39, n. 4, p. 246-258, APR 1 2019. Web of Science Citations: 0.
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 2018. Web of Science Citations: 0.
TAMURA, RODRIGO ESAKI; DE LUNA, IGOR VIEIRA; LANA, MARLOUS GOMES; STRAUSS, BRYAN E. Improving adenoviral vectors and strategies for prostate cancer gene therapy. Clinics, v. 73, n. 1 2018. Web of Science Citations: 2.
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, SEP 19 2017. Web of Science Citations: 25.
MEDRANO, RUAN F. V.; HUNGER, ALINE; CATANI, JOAO P. P.; STRAUSS, BRYAN E. Uncovering the immunotherapeutic cycle initiated by p19Arf and interferon-beta gene transfer to cancer cells: An inducer of immunogenic cell death. ONCOIMMUNOLOGY, v. 6, n. 7 2017. Web of Science Citations: 2.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.