| Full text | |
| Author(s): |
Portela Catani, Joao Paulo
;
Medrano, Ruan F. V.
;
Hunger, Aline
;
Del Valle, Paulo
;
Adjemian, Sandy
;
Zanatta, Daniela Bertolini
;
Kroemer, Guido
;
Costanzi-Strauss, Eugenia
;
Strauss, Bryan E.
Total Authors: 9
|
| Document type: | Journal article |
| Source: | TRANSLATIONAL ONCOLOGY; v. 9, n. 6, p. 565-574, DEC 2016. |
| Web of Science Citations: | 8 |
| Abstract | |
Therapeutic strategies that act by eliciting and enhancing antitumor immunity have been clinically validated as an effective treatment modality but may benefit from the induction of both cell death and immune activation as primary stimuli. Using our AdRGD-PG adenovector platform, we show here for the first time that in situ gene transfer of p19Arf and interferon-beta (IFN beta) in the LLC1 mouse model of lung carcinoma acts as an immunotherapy. Although p19Arf is sufficient to induce cell death, only its pairing with IFN beta significantly inducedmarkers of immunogenic cell death. In situ gene therapy with IFN beta, either alone or in combination with p19Arf, could retard tumor progression, but only the combined treatment was associated with a protective immune response. Specifically in the case of combined intratumoral gene transfer, we identified 167 differentially expressed genes when usingmicroarray to evaluate tumors that were treated in vivo and confirmed the activation of CCL3, CXCL3, IL1 alpha, IL1 beta, CD274, and OSM, involved in immune response and chemotaxis. Histologic evaluation revealed significant tumor infiltration by neutrophils, whereas functional depletion of granulocytes ablated the antitumor effect of our approach. The association of in situ gene therapy with cisplatin resulted in synergistic elimination of tumor progression. In all, in situ gene transfer with p19Arf and IFN beta acts as an immunotherapy involving recruitment of neutrophils, a desirable but previously untested outcome, and this approach may be allied with chemotherapy, thus providing significant antitumor activity and warranting further development for the treatment of lung carcinoma. (AU) | |
| 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: | 12/25380-8 - Analysis of global gene expression regulated by the PRAME/EZH2 complex as a tool to discover new therapeutic targets against Cancer |
| Grantee: | Sandy Adjemian Portela Catani |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| 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 |
| FAPESP's process: | 14/11524-3 - Investigation of antitumor immune response mechanisms induced by combining p19Arf and IFN beta gene transfer |
| Grantee: | João Paulo Portela Catani |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| 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 |