title: Development and Evaluation of Biodegradable Particles Coloaded With Antigen and the Toll-Like Receptor Agonist, Pentaerythritol Lipid A, as a Cancer Vaccine.
abstract: Immune adjuvants are important components of current and prospective cancer vaccines. In this study, we aimed at evaluating the use of a synthetic lipid A derivative, pentaerythritol lipid A (PET lipid A), loaded into poly(lactic-co-glycolic acid) particles, as a potential cancer vaccine adjuvant. 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.
authors.affiliation: Division of Pharmaceutics and Translational Therapeutics, University of Iowa College of Pharmacy, Iowa City, Iowa 52242.
authors.forename: Kawther K
authors.initials: KK
authors.lastname: Ahmed
authors.affiliation: Division of Pharmaceutics and Translational Therapeutics, University of Iowa College of Pharmacy, Iowa City, Iowa 52242.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Geary
authors.affiliation: Division of Pharmaceutics and Translational Therapeutics, University of Iowa College of Pharmacy, Iowa City, Iowa 52242. Electronic address: aliasger-salem@uiowa.edu.
authors.forename: Aliasger K
authors.initials: AK
authors.lastname: Salem
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D000941:Antigens / Q000737:chemistry* / Q000276:immunology; D001672:Biocompatible Materials / Q000737:chemistry*; D019496:Cancer Vaccines / Q000737:chemistry* / Q000276:immunology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D019344:Lactic Acid / Q000737:chemistry; D008050:Lipid A / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011409:Propylene Glycols / Q000737:chemistry* / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D001672:Biocompatible Materials; D019496:Cancer Vaccines; D016207:Cytokines; D008050:Lipid A; D011409:Propylene Glycols; D051193:Toll-Like Receptors; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin; C008783:pentaerythritol
keywords: PET lipid A; cancer vaccine; vaccine adjuvants