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J Control Release. 2018 Feb 28;272:72-82. doi: 10.1016/j.jconrel.2018.01.004. Epub 2018 Jan 8.

Co-delivery of tumor antigen and dual toll-like receptor ligands into dendritic cell by silicon microparticle enables efficient immunotherapy against melanoma.

Author information

1
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
2
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
3
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
4
Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address: rwang3@houstonmethodist.org.

Abstract

Despite the importance and promise of cancer vaccines for broader prevention and treatment of cancer, limited clinical responses are observed, suggesting that key rational designs are required for inducing potent immune responses against cancer. Here we report a mesoporous silicon vector (MSV) as a multi-functional microparticle for formulating an efficient cancer vaccine composed of B16 melanoma derived-tyrosinase related protein 2 (TRP2) peptide and dual toll-like receptor (TLR) agonists. We demonstrated that MSV microparticles protected the peptide from rapid degradation for prolonged antigen presentation to immune cells. Moreover, MSV enabled co-delivery of two different TLR agonists [CpG oligonucleotide and monophosphoryl lipid A (MPLA)] along with TRP2 peptide into the same dendritic cell (DC), thus increasing the efficiency and capacity of DCs to induce potent TRP2-specifc CD8+ T cell responses against B16 melanoma. Furthermore, this MSV-based DC vaccine could significantly prolong the median survival of tumor-bearing mice by orchestrating effective host immune responses involving CD8+ T cells, CD4+ T cells and macrophages. Our study provides rational and potentially translational approach to develop durable and potent immunotherapy for patients with cancer by delivering various combinations of tumor antigens, neoantigens and innate immune agonists.

KEYWORDS:

Cancer vaccine; Dual TLR signaling; Melanoma immunotherapy; Mesoporous silicon microparticles; TRP2 peptide

PMID:
29325699
PMCID:
PMC5825289
DOI:
10.1016/j.jconrel.2018.01.004
[Indexed for MEDLINE]
Free PMC Article

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