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

Autor(es)

Da-Costa, R. C. ^[1] ; Vieira, I. L. ^[1] ; Hunger, A. ^{[1, 2]} ; Tamura, R. E. ^{[3, 1]} ; Strauss, B. E. ^[1]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 53, n. 3 2020.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 13/25167-5 - Transferência gênica de p19Arf e interferon-beta: delineando a importância de sua combinação em modelos murinos de terapia gênica do câncer
• Beneficiário: Bryan Eric Strauss
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/10656-5 - Avaliação dos mecanismos moleculares das vias de p53/ARF e IFN-beta envolvidos com a resposta de células de melanoma ao tratamento com os transgenes p19Arf e IFN-beta.
• Beneficiário: Aline Hunger Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/18197-3 - Investigação dos efeitos angiogênicos diretos e parácrinos, após transferência gênica mediada por vetores adenovirais portadores de Interferon-beta no melanoma murino
• Beneficiário: Igor de Luna Vieira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/21256-8 - Combinação de agentes quimioterápicos e vetores adenovirais expressando p53 na terapia contra o câncer de próstata
• Beneficiário: Rodrigo Esaki Tamura
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/26580-9 - Terapia gênica do câncer: alinhamento estratégico para estudos translacionais
• Beneficiário: Bryan Eric Strauss
• Modalidade de apoio: Auxílio à Pesquisa - Temático