Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\C4144633
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Neuro+Oncol
2014 ; 16
(Suppl 3
): iii42
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
VSTAT120 REDUCES THE INNATE INFLAMMATORY RESPONSE TO INFECTION AND ENHANCES
ONCOLYTIC VIRAL THERAPY FOR GLIOBLASTOMA
#MMPMIDC4144633
Kaur B
; Meisen WH
; Hardcastle J
; Wojton J
; Wohleb E
; Alvarez-Breckenridge C
; Pow-anpongkul P
; Godbout J
; Kaur B
Neuro Oncol
2014[Jul]; 16
(Suppl 3
): iii42
PMIDC4144633
show ga
BACKGROUND: A major barrier to oncolytic virus (OV) efficacy for the treatment of
Glioblastoma is the innate immune response; this response limits virus
replication and reduces tumor cell destruction. Our lab developed a novel OV,
RAMBO, which expresses the anti-angiogenic fragment Vasculostatin (Vstat120). In
addition to its anti-angiogenic effects, we observe the RAMBO virus replicates
more efficiently and persists longer in vivo than a control virus (rHSVQ1). The
primary objective of this study is to investigate the effects RAMBO directed
Vstat120 expression on microglia/macrophage activation and OV efficacy. METHODS:
Mice bearing intracranial tumors were treated with RAMBO, rHSVQ1, or PBS, and
flow cytometry utilized to examine monocyte/microglia activation/recruitment.
Coculture of i9nfected glioma cells with microglia were utilized in in vitro
experiemnts. Cytokines were analyzed via qPCR and ELISA. Virus replication was
determined by plaque forming unit (PFU) assays. RESULTS: Treatment of
intracranial tumors with OV resulted in significant monocyte infiltration into
the tumor. Surprisingly, this infiltration was reduced 4.5 fold in tumors treated
with the RAMBO virus as compared to rHSVQ1 (p < 0.05). Infiltrating monocytes
from RAMBO treated tumors had significantly less MHCII, Ly6C, and CD86 than
rHSVQ1 treated tumors (p < 0.05). The microglia of RAMBO treated tumors had
significantly less MHCII and CD206 expression than those treated with rHSVQ1 (p<
0.05). To further examine the interaction of Vstat120 with microglia/monocytes we
developed a coculture system with murine microglia and infected human glioma
cells. Glioma cells were treated with PBS, rHSVQ1, or RAMBO and cocultured with
microglia. We observed a 75-fold induction of TNF-? expression in microglia
cultured with rHSVQ1 infected glioma cells compared to untreated microglia (p <
0.05). Interestingly, we observed a 3.4-fold reduction in microglia TNF-?
expression in RAMBO treated cocultures compared to rHSVQ1 cocultures (p < 0.01).
Consistent with this ELISA confirmed a 6.9 fold decrease in microglia TNF-?
secretion (p < 0.01), and virus titers revealed a 2.6 fold increase in infectious
virus in RAMBO Vs eHSVQ1 treated cocultures (p < 0.01). Cocultures treated with a
microglia (murine) specific TNF-? blocking antibody rescued the differences in
viral replication between rHSVQ1 and RAMBO virus titers. There was no difference
in virus replication of glioma cells or microglia alone. These results suggest
Vstat120 reduces inflammation and enhances OV replication in part through the
suppression of TNF-? expression/secretion on microglia/monocytes. This transient
suppression of the microglia/monocyte inflammatory response enhances OV
replication and promotes anti-tumor efficacy. CONCLUSIONS: Vasculostatin affects
macrophage recruitment and activity to improve viral replication and efficacy.
SECONDARY CATEGORY: Immunobiology & Immunotherapy.