The anti-tumor response to toll-like receptor 7 agonists

Steven Andrew Broomfield

    Research output: ThesisDoctoral Thesis

    410 Downloads (Pure)

    Abstract

    challenging and potential candidate for therapy in the form of TLR7 agonist treatment. We first investigated the in vitro antitumor efficacy of a range of TLR7 agonists and determined their mode of action (apoptotic/necrotic). We also examined the expression of TLR7 by mesothelioma cell lines and determined their capacity to respond directly to TLR stimulation. We next examined the in vivo anti-tumor activity of the various TLR7 agonists, and focussing on imiquimod, determined the cytotoxic and immunological requirements for the antitumor response. Additionally, we explored some limits to imiquimod therapy and investigated the use of agonistic anti-CD40 antibody immunotherapy to improve responses. Finally, we examined the effectiveness of imiquimod, either alone or in combination, to mount a systemic anti-tumor response against distal tumor. We found that TLR7 agonists induced potent cytotoxicity via apoptosis in vitro, and that AB1-HA and various other tumor cell lines, including human mesothelioma, were found to express TLR7. This suggested a mechanism utilizing viral-like apoptosis that could be potentially applied in vivo against a TLR7-expressing solid tumor as a method of mimicking viral infection...
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2009

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