TY - JOUR
T1 - Malignant Glioma Therapy by Vaccination with Irradiated C6 Cell-Derived Microvesicles Promotes an Antitumoral Immune Response
AU - Pineda, Benjamín
AU - Sánchez García, Francisco Javier
AU - Olascoaga, Nora Karen
AU - Pérez de la Cruz, Verónica
AU - Salazar, Alelí
AU - Moreno-Jiménez, Sergio
AU - Hernández Pedro, Norma
AU - Márquez-Navarro, Adrián
AU - Ortiz Plata, Alma
AU - Sotelo, Julio
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/9/4
Y1 - 2019/9/4
N2 - 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. Pineda et al. characterized and used irradiated C6 cell-derived microvesicles (IR-MVs) to demonstrate that IR-MV-based vaccination can elicit an antitumoral immune response against malignant glioma. They propose that IR-MV could be used as a therapeutic modality for the treatment of glioblastoma patients.
AB - 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. Pineda et al. characterized and used irradiated C6 cell-derived microvesicles (IR-MVs) to demonstrate that IR-MV-based vaccination can elicit an antitumoral immune response against malignant glioma. They propose that IR-MV could be used as a therapeutic modality for the treatment of glioblastoma patients.
KW - antitumor immune response
KW - malignant glioma
KW - microvesicles
KW - vaccination
UR - http://www.scopus.com/inward/record.url?scp=85067192675&partnerID=8YFLogxK
U2 - 10.1016/j.ymthe.2019.05.016
DO - 10.1016/j.ymthe.2019.05.016
M3 - Artículo
C2 - 31204210
SN - 1525-0016
VL - 27
SP - 1612
EP - 1620
JO - Molecular Therapy
JF - Molecular Therapy
IS - 9
ER -