Improving adenoviral vectors and strategies for prostate cancer gene therapy

Autor(es)

Tamura, Rodrigo Esaki ^[1] ; de Luna, Igor Vieira ^[1] ; Lana, Marlous Gomes ^[1] ; Strauss, Bryan E. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Hosp Clin HCFMUSP, ICESP, Lab Vetores Virais, Ctr Invest Translac Oncol, Fac, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: Clinics; v. 73, n. 1 2018.
• Citações Web of Science: 2

Resumo

Gene therapy has been evaluated for the treatment of prostate cancer and includes the application of adenoviral vectors encoding a suicide gene or oncolytic adenoviruses that may be armed with a functional transgene. In parallel, versions of adenoviral vector expressing the p53 gene (Ad-p53) have been tested as treatments for head and neck squamous cell carcinoma and non-small cell lung cancer. Although Ad-p53 gene therapy has yielded some interesting results when applied to prostate cancer, it has not been widely explored, perhaps due to current limitations of the approach. To achieve better functionality, improvements in the gene transfer system and the therapeutic regimen may be required. We have developed adenoviral vectors whose transgene expression is controlled by a p53-responsive promoter, which creates a positive feedback mechanism when used to drive the expression of p53. Together with improvements that permit efficient transduction, this new approach was more effective than the use of traditional versions of Ad-p53 in killing prostate cancer cell lines and inhibiting tumor progression. Even so, gene therapy is not expected to replace traditional chemotherapy but should complement the standard of care. In fact, chemotherapy has been shown to assist in viral transduction and transgene expression. The cooperation between gene therapy and chemotherapy is expected to effectively kill tumor cells while permitting the use of reduced chemotherapy drug concentrations and, thus, lowering side effects. Therefore, the combination of gene therapy and chemotherapy may prove essential for the success of both approaches. (AU)

• 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
• Processo FAPESP: 12/05066-7 - Utilização de shRNA anti-hexon e anti-IVa2 durante a produção de vírus adeno-associado como estratégia de eliminar adenovírus helper: Prova de princípio
• Beneficiário: Marlous Vinícius Gomes Lana
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• 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: 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