| Full text | |
| Author(s): |
Vieira Medrano, Ruan Felipe
[1]
;
Portela Catani, Joao Paulo
[1]
;
Ribeiro, Aline Hunger
[1]
;
Tomaz, Samanta Lopes
[2]
;
Merkel, Christian A.
[3]
;
Costanzi-Strauss, Eugenia
[4]
;
Strauss, Bryan E.
[1]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Viral Vector Lab, Ctr Invest Translac Oncol LIM24, Av Dr Arnaldo 251, 8th Floor, BR-01246000 Sao Paulo, SP - Brazil
[2] Univ Fed Sao Paulo, Escola Paulista Med, Sao Paulo - Brazil
[3] Univ Sao Paulo, Fac Med, Anim Care Facil, Sao Paulo - Brazil
[4] Univ Sao Paulo, Gene Therapy Lab, Inst Ciencias Biomed 1, Sao Paulo - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | CANCER IMMUNOLOGY IMMUNOTHERAPY; v. 65, n. 4, p. 371-382, APR 2016. |
| Web of Science Citations: | 9 |
| Abstract | |
Previously, we combined p19(Arf) (Cdkn2a, tumor suppressor protein) and interferon beta (IFN-beta, immunomodulatory cytokine) gene transfer in order to enhance cell death in a murine model of melanoma. Here, we present evidence of the immune response induced when B16 cells succumbing to death due to treatment with p19(Arf) and IFN-beta are applied in vaccine models. Use of dying cells for prophylactic vaccination was investigated, identifying conditions for tumor-free survival. After combined p19(Arf) and IFN-beta treatment, we observed immune rejection at the vaccine site in immune competent and nude mice with normal NK activity, but not in NOD-SCID and dexamethasone immunosuppressed mice (NK deficient). Combined treatment induced IL-15, ULBP1, FAS/APO1 and KILLER/DR5 expression, providing a mechanism for NK activation. Prophylactic vaccination protected against tumor challenge, where markedly delayed progression and leukocyte infiltration were observed. Analysis of primed lymphocytes revealed secretion of TH1-related cytokines and depletion protocols showed that both CD4(+) and CD8(+) T lymphocytes are necessary for immune protection. However, application of this prophylactic vaccine where cells were treated either with IFN-beta alone or combined with p19(Arf) conferred similar immune protection and cytokine activation, yet only the combination was associated with increased overall survival. In a therapeutic vaccine protocol, only the combination was associated with reduced tumor progression. Our results indicate that by harnessing cell death in an immunogenic context, our p19(Arf) and IFN-beta combination offers a clear advantage when both genes are included in the vaccine and warrants further development as a novel immunotherapy for melanoma. (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: | 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 |