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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Cancer+Immunol+Res
2015 ; 3
(9
): 1096-107
Nephropedia Template TP
gab.com Text
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English Wikipedia
Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with
Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive
Pancreatic Tumors
#MMPMID26134178
Manuel ER
; Chen J
; D'Apuzzo M
; Lampa MG
; Kaltcheva TI
; Thompson CB
; Ludwig T
; Chung V
; Diamond DJ
Cancer Immunol Res
2015[Sep]; 3
(9
): 1096-107
PMID26134178
show ga
Bacterial-based therapies are emerging as effective cancer treatments and hold
promise for refractory neoplasms, such as pancreatic ductal adenocarcinoma
(PDAC), which has not shown significant improvement in therapy for more than 25
years. Using a novel combination of shIDO-ST, a Salmonella-based therapy
targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with
an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed
extended survival with frequent total regression of autochthonous and orthotopic
PDAC tumors. This observation was associated with migration and accumulation of
activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was
not seen using a scrambled control (shScr-ST). Purified splenic PMNs from
PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able
to kill tumor targets ex vivo through mechanisms involving FasL and serine
proteases. In addition, CD8(+) T cells were observed to contribute to late
control of pancreatic tumors. Collectively, our data demonstrate that entry of
shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated
by PEGPH20-mediated HA removal, further highlighting an important component of
effective treatment for PDAC.