title: Design and Development of Immunomodulatory Antigen Delivery Systems Based on Peptide/PEG-PLA Conjugate for Tuning Immunity.
abstract: Cancer vaccines are considered to be a promising tool for cancer immunotherapy. However, a well-designed cancer vaccine should combine a tumor-associated antigen (TAA) with the most effective immunomodulatory agents and/or delivery system to provoke intense immune responses against the TAA. In the present study, we introduced a new approach by conjugating the immunomodulatory molecule LD-indolicidin to the hydrophilic chain end of the polymeric emulsifier poly(ethylene glycol)-polylactide (PEG-PLA), allowing the molecule to be located close to the surface of the resulting emulsion. A peptide/polymer conjugate, named LD-indolicidin-PEG-PLA, was synthesized by conjugation of the amine end-group of LD-indolicidin to the N-hydroxysuccinimide-activated carboxyl end-group of PEG. As an adjuvant for cancer immunotherapeutic use, TAA vaccine candidate formulated with the LD-indolicidin-PEG-PLA-stabilized squalene-in-water emulsion could effectively help to elicit a T helper (Th)1-dominant antigen-specific immune response as well as antitumor ability, using ovalbumin (OVA) protein/EG7 cells as a TAA/tumor cell model. Taken together, these results open up a new approach to the development of immunomodulatory antigen delivery systems for vaccine adjuvants and cancer immunotherapy technologies.
authors.affiliation: Max Mousseron Institute of Biomolecules, UMR CNRS 5247, University of Montpellier, Faculty of Pharmacy , 34093 Montpellier Cedex 5, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Coumes
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , 35053 Miaoli, Taiwan.
authors.forename: Chiung-Yi
authors.initials: CY
authors.lastname: Huang
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , 35053 Miaoli, Taiwan.
authors.forename: Chung-Hsiung
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Max Mousseron Institute of Biomolecules, UMR CNRS 5247, University of Montpellier, Faculty of Pharmacy , 34093 Montpellier Cedex 5, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Coudane
authors.affiliation: Max Mousseron Institute of Biomolecules, UMR CNRS 5247, University of Montpellier, Faculty of Pharmacy , 34093 Montpellier Cedex 5, France.|Institut National de la Santé et de la Recherche Médicale, 34000 Montpellier, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Domurado
authors.affiliation: Institut Europeen des Membranes, UMR CNRS 5635, University of Montpellier , 34095 Montpellier, France.
authors.forename: Suming
authors.initials: S
authors.lastname: Li
authors.affiliation: Max Mousseron Institute of Biomolecules, UMR CNRS 5247, University of Montpellier, Faculty of Pharmacy , 34093 Montpellier Cedex 5, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Darcos
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes , 35053 Miaoli, Taiwan.|Graduate Institute of Immunology, China Medical University , 40402 Taichung, Taiwan.
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Huang
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D019496:Cancer Vaccines / Q000737:chemistry / Q000276:immunology; D016503:Drug Delivery Systems; D004655:Emulsions; D005260:Female; D007109:Immunity / Q000187:drug effects*; D056747:Immunomodulation; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D010047:Ovalbumin / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013185:Squalene / Q000737:chemistry; D013388:Succinimides / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D019496:Cancer Vaccines; D004655:Emulsions; D010455:Peptides; D013388:Succinimides; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; C073143:indolicidin; D011092:Polyethylene Glycols; D013185:Squalene; D010047:Ovalbumin; C001426:N-hydroxysuccinimide