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Central Tolerance Blockade to Augment Checkpoint Immunotherapy in Melanoma

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Technical Report,15 Aug 2015,14 Aug 2016

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The University of North Carolina at Chapel Hill Chapel Hill United States

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We recently found that a new agent anti-RANKL antibody rescues melanoma-fighting T cells from thymus elimination. Anti-RANK L antibody is different from other cancer immunotherapies because of this unique mode of action. By itself, anti-RANKL antibody improves the survival of mice injected with melanoma cells. Because anti-RANKL antibody and checkpoint inhibitors work in distinct, non-redundant ways, we hypothesize that anti-RANKL antibody will increase the effectiveness of checkpoint inhibitors in rejecting melanoma tumors in mice and humans. This grant proposal will provide critical information needed to bring anti-RANKL antibody to the clinic for treating advanced melanoma patients. To date, our findings include RANKL is expressed at high levels on human thymocytes RANK is expressed at higher levels in medullary thymic epithelial cells mTECs than in cortical thymic epithelial cells cTECs. These finding lend preclinical evidence for using anti-RANKL antibody to block central tolerance.

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