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Mol Ther ; 27(9): 1612-1620, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31204210

RESUMO

Glioblastoma is the most common and malignant tumor of the CNS, with a mean survival of 14 months after diagnosis. Its unfavorable prognosis reveals the need for novel therapies. It is known that radiation can induce a systemic antitumor effect. Tumor cells produce and release microvesicles in response to cell damage such as radiation. Microvesicles contain a plethora of bioactive molecules, including antigens involved in modulation of the immune response. In this study, we characterized and evaluated irradiated C6 cell-derived microvesicles as a therapeutic vaccination in C6 malignant glioma. Cultured C6 glioma cells were irradiated with a single dose of 50 Gy to obtain the microvesicles. Subcutaneous implantation of C6 cells was performed when the tumor reached 2 cm in diameter, and non-irradiated and irradiated C6 cell-derived microvesicles were administered subcutaneously. Tumor growth, apoptosis, and immunophenotypes were determined. Reduction of tumor volume (more than 50%) was observed in the group treated with irradiated C6 cell-derived microvesicles compared with the control (p = 0.03). The percentages of infiltrative helper, cytotoxic, and regulatory T lymphocytes as well as apoptotic cells were increased in tumors from immunized rats compared with controls. These findings make microvesicle-based vaccination a promising immunotherapeutic approach against glioblastoma.


Assuntos
Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Vacinas Anticâncer/imunologia , Micropartículas Derivadas de Células/imunologia , Glioblastoma/imunologia , Glioblastoma/terapia , Animais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Vacinas Anticâncer/administração & dosagem , Linhagem Celular Tumoral , Micropartículas Derivadas de Células/efeitos da radiação , Modelos Animais de Doenças , Glioblastoma/mortalidade , Glioblastoma/patologia , Imunidade , Imunização , Ratos , Resultado do Tratamento , Carga Tumoral/imunologia
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