Glioma Immunotherapy With Combined Autologous Tumor Cell and Endothelial Cell Vaccine In Vivo

Abstract

Combined vaccines containing GL261 murine glioma cells and F-2 murine endothelial cells fixed with glutaraldehyde-phosphate buffered saline were injected into the intradermal tissue of the tail base of C57BL/6 mice. After the vaccination, GL261 cells were injected subcutaneously into the left flank of the mice. Vaccination with fixed F-2 cells induced the development of relatively high amounts of interferon-gamma-releasing cells after in vitro re-stimulation with vascular endothelial growth factor-receptor 2 peptide. Tumor growth was inhibited after preventive use of the combined vaccine, prepared from GL261 and F-2 cells. Tumor specimens obtained from the combined vaccine group in a therapeutic experiment showed significantly decreased vessel count. Glioma immunotherapy with a combined vaccine prepared from tumor cells and endothelial cells might represent a new clinical strategy, as such combinations may theoretically affect both high-grade glioma cells and their environment.

Impact of Immunotherapy in the Treatment of Glioblastoma

“…In addition, an interesting in vivo study assessed the effect of a combined vaccine, prepared from GBM and endothelial cells, on glioma-bearing mice. While tumor growth inhibition was seen only in the preventive use of the combined vaccine, a significantly decrease in vessel account was verified in the tumor upon the therapeutic experiment with that vaccine [37].…”

“…Interestingly, an immunotherapy strategy combining cellular vaccines (prepared from autologous GL261 murine glioma cells and F-2 murine endothelial cells) was tested on glioma-bearing mice. Such preclinical study revealed that combined vaccine significantly decreased tumor growth and vessel account, thus representing an expecting strategy capable to target both GBM cells and their microenvironment [37].…”

“…As it is well known, angiogenesis is a hallmark of GBM that facilitates tumor progression and invasiveness. Based on that, HUVEC vaccination consists of an endovascular targeting immunotherapy intended to trigger an antiangiogenic response, upon presentation of HUVEC antigen to the immune system [14,37]. To the best of our knowledge, only two preliminary CT was conducted with HUVEC vaccines for recurrent GBM patients, whose clinical outcomes were promising without serious adverse events associated [14,36,38].…”

LPA4-Mediated Vascular Network Formation Increases the Efficacy of Anti–PD-1 Therapy against Brain Tumors

“…Cell culture GL261 (mouse glioblastoma) was kindly provided from Dr. Shingo Takano (Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan) without further authentication (18). LLC was purchased from RIKEN Cell Bank.…”

“…Finally, we tested the effect of LPA in a xenograft model using primary human GMB cells (GDC40; ref. 18). We transplanted 2 Â 10 5 GDC40 cells into brains of NOD/SCID mice.…”