Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/184763
Title: Manipulating TLR signaling increases the anti-tumor T Cell response induced by viral cancer therapies
Author: Rojas, Juan J.
Sampath, Padma
Bonilla, Braulio
Ashley, Alexandra
Hou, Weizhou
Byrd, Daniel
Thorne, Steve H.
Keywords: Apoptosi
Immunoteràpia
Càncer
Necrosi
Apoptosis
Immunotheraphy
Cancer
Necrosis
Issue Date: 12-Apr-2016
Publisher: Elsevier
Abstract: The immune response plays a key role in enhancing the therapeutic activity of oncolytic virotherapies. However, to date, investigators have relied on inherent interactions between the virus and the immune system, often coupled to the expression of a single cytokine transgene. Recently, the importance of TLR activation in mediating adaptive immunity has been demonstrated. We therefore sought to influence the type and level of immune response raised after oncolytic vaccinia therapy through manipulation of TLR signaling. Vaccinia naturally activates TLR2, associated with an antibody response, whereas a CTL response is associated with TLR3-TRIF-signaling pathways. We manipulated TLR signaling by vaccinia through deglycosylation of the viral particle to block TLR2 activation and expression of a TRIF transgene. The resulting vector displayed greatly reduced production of anti-viral neutralizing antibody as well as an increased anti-tumor CTL response. Delivery in both naive and pre-treated mice was enhanced and immunotherapeutic activity dramatically improved.
Note: Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2016.03.017
It is part of: Cell Reports, 2016, vol. 15, p. 264-273
URI: http://hdl.handle.net/2445/184763
Related resource: https://doi.org/10.1016/j.celrep.2016.03.017
ISSN: 2211-1247
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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