Response of human melanoma cell lines to interferon-beta gene transfer mediated by a modified adenoviral vector

Author(s)

David, Taynah I. P. ^[1] ; Cerqueira, Otto L. D. ^[1] ; Lana, Marlous G. ^[1] ; Medrano, V, Ruan F. ; Hunger, Aline ^{[2, 3]} ; Strauss, Bryan E. ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Ctr Invest Translat Oncol, Inst Canc Estado Sao Paulo, Lab Vetores Virais, Av Dr Arnaldo 251, 8th Floor, Sao Paulo, SP - Brazil

^[2] Medrano, Ruan F., V, Univ Sao Paulo, Fac Med, Ctr Invest Translat Oncol, Inst Canc Estado Sao Paulo, Lab Vetores Virais, Av Dr Arnaldo 251, 8th Floor, Sao Paulo, SP - Brazil

^[3] Cristalia, Biotecnol Unidade 1, Rodoviaria SP 147, Itapira, SP - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 OCT 21 2020.
• Web of Science Citations: 1

Abstract

Since melanomas often retain wild type p53, we developed an adenoviral vector, AdRGD-PG, which provides robust transduction and transgene expression in response to p53. Previously, this vector was used for interferon-beta gene transfer in mouse models of melanoma, resulting in control of tumor progression, but limited cell killing. Here, the AdRGD-PG-hIFN beta vector encoding the human interferon-beta cDNA (hIFN beta) was used to transduce human melanoma cell lines SK-MEL-05 and SK-MEL-147 (both wild type p53). In vitro, cell death was induced in more than 80% of the cells and correlated with elevated annexinV staining and caspase 3/7 activity. Treatment with hIFN beta promoted cell killing in neighboring, non-transduced cells, thus revealing a bystander effect. In situ gene therapy resulted in complete inhibition of tumor progression for SK-MEL-147 when using nude mice with no evidence of hepatotoxicity. However, the response in Nod-Scid mice was less robust. For SK-MEL-05, tumor inhibition was similar in nude and Nod-Scid mice and was less efficient than seen for SK-MEL-147, indicating both cell type and host specific responses. The AdRGD-PG-hIFN beta vector provides extensive killing of human melanoma cells in vitro and a potent anti-tumor effect in vivo. This study provides a critical advance in the development of our melanoma gene therapy approach. (AU)

• FAPESP's process: 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
• Grantee: Otto Luiz Dutra Cerqueira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 10/15025-0 - Construction and characterization of adenoviral vectors carrying the human interferon beta cDNA
• Grantee: Taynah Ibrahim Picolo David
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 12/05066-7 - Use of shRNA anti-hexon e anti-IVa2 during the production of adeno-associated virus as a strategy for eliminating helper adenovirus: Proof of principle
• Grantee: Marlous Vinícius Gomes Lana
• Support Opportunities: Scholarships in Brazil - Master
• 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: 15/26580-9 - Cancer gene therapy: strategic positioning for translational studies
• Grantee: Bryan Eric Strauss
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/09474-5 - Association of the immunotherapy mediated by p19Arf and Interferon-beta gene transfer with immunogenic cell death induced by the chemotherapic doxorubicin for the treatment of cancer
• Grantee: Ruan Felipe Vieira Medrano
• Support Opportunities: Scholarships in Brazil - Doctorate