Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5536572 | Vaccine | 2017 | 8 Pages |
Abstract
The lipid calcium phosphate nanoparticle is a versatile platform capable of encapsulating a wide range of phosphorylated molecules from single nucleotides to pDNA. The use of this platform has shown great success as an immunotherapeutic vaccine carrier, capable of delivering co-encapsulated phosphorylated adjuvants and peptides. Three potent vaccine formulations were investigated for anti-cancer efficacy. The phosphorylated adjuvants, CpG, 2â²3â²cGAMP, and 5â²pppdsRNA were co-encapsulated with a model phosphorylated tumor specific peptide antigen (p-AH1-A5). The anti-cancer efficacy of these adjuvants was assessed using an orthotopic colorectal liver metastasis model based on highly aggressive and metastatic CT-26 FL3 cells implanted into the cecum wall. The results clearly indicate that the RIG-1 ligand, 5â²pppdsRNA, co-encapsulated with the p-AH1-A5 peptide antigen greatly reduced the growth rate of the primary colon cancer as well as arrested the establishment of liver metastasis in comparison to the other adjuvant formulations and unvaccinated controls. Further evaluation of the immune cell populations within the primary tumor confirms the ability of the 5â²pppdsRNA adjuvant to boost the adaptive CD8+ T-cell population, while not inciting increased populations of immune suppressive cell types such as T-regulatory cells or myeloid derived suppressor cells. Furthermore, to our knowledge this is the first study to investigate the anti-cancer efficacy of a specific RIG-1 receptor ligand, 5â²pppdsRNA, alongside more established TLR 9 (CpG) and STING (2â²3â²cGAMP) adjuvants in a cancer vaccine. The 5â²pppdsRNA vaccine formulation can be a potent immunotherapy, especially when combined with agents that remodel the immune suppressive microenvironment of the tumor.
Keywords
1,2-Dioleoyl-sn-glycero-3-phosphateDLSRFPDSPEPBSDOTAPN-hydroxysuccinimideenzyme linked immunospot assayELISPOTLCPDOPANHSALTCpGDAPI1,2-dioleoyl-3-trimethylammonium-propane4′,6-diamidino-2-phenylindoleASTAspartate aminotransferaseAlanine aminotransferaseTembio-layer interferometryBUNBLIColorectal cancerPhosphate buffered salineColorectal liver metastasisTransmission electron microscopyblood urea nitrogenVaccineDynamic Light Scatteringred fluorescent proteinpolyethylene glycolPEGCRC
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Authors
Tyler J. Goodwin, Leaf Huang,