Vaccine therapy with dendritic cells transfected with Il13ra2 mRNA for glioma in mice

Author:

Saka Makoto1,Amano Takayuki1,Kajiwara Koji1,Yoshikawa Koichi1,Ideguchi Makoto1,Nomura Sadahiro1,Fujisawa Hirosuke1,Kato Shoichi1,Fujii Masami1,Ueno Koji2,Hinoda Yuji2,Suzuki Michiyasu1

Affiliation:

1. Departments of Neurosurgery and

2. Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan

Abstract

Object The Il13ra2 gene is often overexpressed in brain tumors, making Il13ra2 one of the vaccine targets for immunotherapy of glioma. In this study, using a mouse glioma model, the authors tested the hypothesis that vaccination using dendritic cells transfected with Il13ra2 mRNA induces strong immunological antitumor effects. Methods A plasmid was constructed for transduction of the mRNAs transcribed in vitro into dendritic cells. This was done to transport the intracellular protein efficiently into major histocompatibility complex class II compartments by adding a late endosomal/lysosomal sorting signal to the Il13ra2 gene. The dendritic cells transfected with this Il13ra2 mRNA were injected intraperitoneally into the mouse glioma model at 3 and 10 days after tumor cell implantation. The antitumor effects were estimated based on the survival rate, results of histological analysis, and immunohistochemical findings for immune cells. Results The group treated by vaccination therapy with dendritic cells transfected with Il13ra2 mRNA survived significantly longer than did the control groups. Immunohistochemical analysis revealed that greater numbers of T lymphocytes containing CD4+ and CD8+ T cells were found in the group vaccinated with dendritic cells transfected with Il13ra2 mRNA. Conclusions These results demonstrate the therapeutic potential of vaccination with dendritic cells transfected with Il13ra2 mRNA for the treatment of malignant glioma.

Publisher

Journal of Neurosurgery Publishing Group (JNSPG)

Subject

Genetics,Animal Science and Zoology

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