| Full text | |
| 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]
Total Authors: 6
|
| 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
Total Affiliations: 3
|
| 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 |