| Full text | |
| Author(s): Show less - |
Medrano, Ruan F., V
;
Salles, Thiago A.
;
Dariolli, Rafael
;
Antunes, Fernanda
;
Feitosa, Valker A.
;
Hunger, Aline
;
Catani, Joao P. P.
;
Mendonca, Samir A.
;
Tamura, Rodrigo E.
;
Lana, Marlous G.
;
Rodrigues, Elaine G.
;
Strauss, Bryan E.
Total Authors: 12
|
| Document type: | Journal article |
| Source: | SCIENTIFIC REPORTS; v. 12, n. 1, p. 14-pg., 2022-08-10. |
| Abstract | |
Balancing safety and efficacy is a major consideration for cancer treatments, especially when combining cancer immunotherapy with other treatment modalities such as chemotherapy. Approaches that induce immunogenic cell death (ICD) are expected to eliminate cancer cells by direct cell killing as well as activation of an antitumor immune response. We have developed a gene therapy approach based on p19Arf and interferon-beta gene transfer that, similar to conventional inducers of ICD, results in the release of DAMPS and immune activation. Here, aiming to potentiate this response, we explore whether association between our approach and treatment with doxorubicin (Dox), a known inducer of ICD, could further potentiate treatment efficacy without inducing cardiotoxicity, a critical side effect of Dox. Using central composite rotational design analysis, we show that cooperation between gene transfer and chemotherapy killed MCA205 and B16F10 cells and permitted the application of reduced viral and drug doses. The treatments also cooperated to induce elevated levels of ICD markers in MCA205, which correlated with improved efficacy of immunotherapy in vivo. Treatment of subcutaneous MCA205 tumors associating gene transfer and low dose (10 mg/kg) chemotherapy resulted in inhibition of tumor progression. Moreover, the reduced dose did not cause cardiotoxicity as compared to the therapeutic dose of Dox (20 mg/kg). The association of p19Arf/interferon-beta gene transfer and Dox chemotherapy potentiated antitumor response and minimized cardiotoxicity. (AU) | |
| FAPESP's process: | 18/04800-5 - The role of p73 isoforms in the response of B16F10 cells to transduction with adenoviral vectors carrying p19Arf and IFNbeta cDNAs. |
| Grantee: | Fernanda Antunes |
| 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: | 15/26580-9 - Cancer gene therapy: strategic positioning for translational studies |
| Grantee: | Bryan Eric Strauss |
| Support Opportunities: | Research Projects - Thematic Grants |
| 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: | 11/21256-8 - Combination of chemotherapy and adenoviral vectors expressing p53 for the therapy of prostate cancer |
| Grantee: | Rodrigo Esaki Tamura |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| 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: | 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 |