Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25959818
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Direct Activation of STING in the Tumor Microenvironment Leads to Potent and
Systemic Tumor Regression and Immunity
#MMPMID25959818
Corrales L
; Glickman LH
; McWhirter SM
; Kanne DB
; Sivick KE
; Katibah GE
; Woo SR
; Lemmens E
; Banda T
; Leong JJ
; Metchette K
; Dubensky TW Jr
; Gajewski TF
Cell Rep
2015[May]; 11
(7
): 1018-30
PMID25959818
show ga
Spontaneous tumor-initiated T cell priming is dependent on IFN-? production by
tumor-resident dendritic cells. On the basis of recent observations indicating
that IFN-? expression was dependent upon activation of the host STING pathway, we
hypothesized that direct engagement of STING through intratumoral (IT)
administration of specific agonists would result in effective anti-tumor therapy.
After proof-of-principle studies using the mouse STING agonist DMXAA showed a
potent therapeutic effect, we generated synthetic cyclic dinucleotide (CDN)
derivatives that activated all human STING alleles as well as murine STING. IT
injection of STING agonists induced profound regression of established tumors in
mice and generated substantial systemic immune responses capable of rejecting
distant metastases and providing long-lived immunologic memory. Synthetic CDNs
have high translational potential as a cancer therapeutic.
free
free
free
