Central Tolerance Blockade to Augment Checkpoint Immunotherapy in Melanoma
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2016
- Accession Number
- AD1017029
Entities
People
- Maureen A Su
Organizations
- University of North Carolina at Chapel Hill