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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

p19Arf sensitizes B16 melanoma cells to interferon-beta delivered via mesenchymal stem cells in vitro

Full text
Author(s):
Da-Costa, R. C. [1] ; Vieira, I. L. [1] ; Hunger, A. [1, 2] ; Tamura, R. E. [3, 1] ; Strauss, B. E. [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Fac Med, Ctr Invest Translac Oncol LIM24, Inst Canc Estado Sao Paulo, Viral Vector Lab, Sao Paulo, SP - Brazil
[2] Cristalia Prods Quim Farmaceut, Biotecnol Unidade 1, Itapira, SP - Brazil
[3] Univ Fed Sao Paulo, Dept Ciencias Biol, Diadema, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Brazilian Journal of Medical and Biological Research; v. 53, n. 3 2020.
Web of Science Citations: 0
Abstract

The immune stimulatory and anti-neoplastic functions of type I interferon have long been applied for the treatment of melanoma. However, the systemic application of high levels of this recombinant protein is often met with toxicity. An approach that provides localized, yet transient, production of type I interferon may overcome this limitation. We propose that the use of mesenchymal stem cells (MSCs) as delivery vehicles for the production of interferon-beta (IFN beta) may be beneficial when applied together with our cancer gene therapy approach. In our previous studies, we have shown that adenovirus-mediated gene therapy with IFN beta was especially effective in combination with p19Arf gene transfer, resulting in immunogenic cell death. Here we showed that MSCs derived from mouse adipose tissue were susceptible to transduction with adenovirus, expressed the transgene reliably, and yet were not especially sensitive to IFN beta production. MSCs used to produce IFN beta inhibited B16 mouse melanoma cells in a co-culture assay. Moreover, the presence of p19Arf in the B16 cells sensitizes them to the IFN beta produced by the MSCs. These data represent a critical demonstration of the use of MSCs as carriers of adenovirus encoding IFN beta and applied as an anticancer strategy in combination with p19Arf gene therapy. (AU)

FAPESP's process: 13/25167-5 - P19Arf and interferon-beta gene transfer: delineating the importance of their combination in mouse models of cancer gene therapy
Grantee:Bryan Eric Strauss
Support Opportunities: Regular Research Grants
FAPESP's process: 11/10656-5 - Evaluation of the molecular mechanisms of p53/ARF and IFN-beta pathways involved in the the response of melanoma cells to treatment with the p19Arf and IFN-beta transgenes.
Grantee:Aline Hunger Ribeiro
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 16/18197-3 - Investigation of the direct and paracrine angiogenic effects after gene transfer mediated by adenoviral vectors carrying the Interferon-beta in murine melanoma
Grantee:Igor de Luna Vieira
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 11/21256-8 - Combination of chemotherapy and adenoviral vectors expressing p53 for the therapy of prostate cancer
Grantee:Rodrigo Esaki Tamura
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 15/26580-9 - Cancer gene therapy: strategic positioning for translational studies
Grantee:Bryan Eric Strauss
Support Opportunities: Research Projects - Thematic Grants