کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2039834 1073085 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Manipulating TLR Signaling Increases the Anti-tumor T Cell Response Induced by Viral Cancer Therapies
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
پیش نمایش صفحه اول مقاله
Manipulating TLR Signaling Increases the Anti-tumor T Cell Response Induced by Viral Cancer Therapies
چکیده انگلیسی


• Vaccinia surface deglycosylation reduces TLR2 activation and antibody production
• Vaccinia surface deglycosylation protects against a neutralizing antibody
• Vaccinia TRIF expression induces an increased CTL response
• Deglycosylation and TRIF expression enhances oncolytic vaccinia therapeutic effects

SummaryThe 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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 15, Issue 2, 12 April 2016, Pages 264–273
نویسندگان
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