Targeting dendritic cells in lymph node with an antigen peptide-based nanovaccine for cancer immunotherapy

The design of peptide-based subunit vaccine formulations for the direct delivery of tumor antigen peptides (Aps) to dendritic cells (DCs) localized within draining lymph nodes (DLNs) is challenging. Mature DCs (mDCs) are abundantly distributed within DLNs but have dramatically reduced endocytic uptake and antigen-processing abilities, so their role as potential vaccine targets has been largely overlooked. Here we report an ultra-small biocompatible nanovaccine (alpha-Ap-FNP) functionalized by avidly targeting delivery of Ap via the scavenger receptor class B1 (SR-B1) pathway to mDCs. The self-assembly, small size (similar to 30 nm), SR-B1-targeting and optical properties of alpha-Ap-FNP resulted in its efficient Ap loading, substantial LN accumulation, targeting of mDCs and enhanced Ap presentation, and fluorescence trafficking, respectively. We also demonstrate that the alpha-Ap-FNP can be either used alone or encapsulated with CpG oligodeoxynucleotide as a prophylactic and therapeutic vaccine. Thus, the excellent properties of alpha-Ap-FNP provide it potential for clinical applications as a potent nanovaccine for cancer immunotherapy. (C) 2016 Elsevier Ltd. All rights reserved.