Enhancing anti-tumor immunity through local gene delivery to lymph nodes
Dold, Neil M
Jewell, Christopher M
Dold, N.M., Jewell, C.M. Enhancing anti-tumor immunity through local gene delivery to lymph nodes. j. immunotherapy cancer 3, P431 (2015).
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Biodegradable polymer carriers offer attractive features for therapeutic cancer vaccines including delivery of multiple vaccine components, efficient internalization, and sustained release of adjuvants and tumor-associated antigens (TAAs). We previously demonstrated that local delivery of depots containing nucleic acid-based toll-liked receptor agonists (TLRas) to lymph nodes (LNs) potently enhances antigen-specific T cell immunity. Building on this work, we hypothesized that local LN delivery of microparticles loaded with TAA-encoding plasmid DNA (pDNA) and TLRas might drive strong local expression and presentation of antigen by LN-resident antigen presenting cells. These effects could help drive more potent and effective CD8+ T cell functions that slow or stop tumor growth.