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PET Lipid A

Vaxjo ID 285       
Vaccine Adjuvant Name PET Lipid A       
Adjuvant VO ID VO_0005773
Description PET Lipid A is a synthetic TLR-4 agonist that is used as a potential cancer vaccine adjuvant.       
Components Poly(lactic-co-glycolic acid) particles (size range: 250-600 nm) were successfully formulated to include PET lipid A and/or the model tumor antigen, chicken ovalbumin (OVA).It was shown that particulated PET lipid A had a distinct advantage at promoting secretion of the immune potentiating cytokine, IL-12p70, and upregulating key costimulatory surface proteins, CD86 and CD40, in murine dendritic cells in vitro.In a murine tumor model, involving prophylactic vaccination with various permutations of soluble versus particulated formulations of OVA with or without PET lipid A, modest benefit was observed in terms of OVA-specific cell-mediated immune responses when PET lipid A was delivered in particles.These findings translated into a corresponding trend toward increased survival of mice challenged with OVA-expressing tumor cells (E.G7).In terms of translation of safe adjuvants into the clinic, these results promote the concept of delivering toll-like receptor-4 agonists in particles because doing so improves their adjuvant properties, while decreasing the chances of adverse effects due to off-target uptake by nonphagocytic cells.       
Structure Contains an amine-substituted pentaerythritol instead of a glucosamine unit found in natural lipid A, retaining a hexaacylated chain structure.       
Preparation PET Lipid A is prepared using a double emulsion-solvent evaporation method and is loaded into PLGA particles.       
Dosage In the study, PET Lipid A was administered at a dose of 18 µg.       
Function Development and Evaluation of Biodegradable Particles Coloaded With Antigen and the Toll-Like Receptor Agonist, Pentaerythritol Lipid A, as a Cancer Vaccine       
References
Ahmed et al., 2016: Ahmed KK, Geary SM, Salem AK. Development and Evaluation of Biodegradable Particles Coloaded With Antigen and the Toll-Like Receptor Agonist, Pentaerythritol Lipid A, as a Cancer Vaccine. Journal of pharmaceutical sciences. 2016; 105(3); 1173-1179. [PubMed: 26886334].