title: Plasma membrane vesicles decorated with glycolipid-anchored antigens and adjuvants via protein transfer as an antigen delivery platform for inhibition of tumor growth.
abstract: Antigen delivered within particulate materials leads to enhanced antigen-specific immunity compared to soluble administration of antigen. However, current delivery approaches for antigen encapsulated in synthetic particulate materials are limited by the complexity of particle production that affects stability and immunogenicity of the antigen. Herein, we describe a protein delivery system that utilizes plasma membrane vesicles (PMVs) derived from biological materials such as cultured cells or isolated tissues and a simple protein transfer technology. We show that these particulate PMVs can be easily modified within 4 h by a protein transfer process to stably incorporate a glycosylphosphatidylinositol (GPI)-anchored form of the breast cancer antigen HER-2 onto the PMV surface. Immunization of mice with GPI-HER-2-modified-PMVs induced strong HER-2-specific antibody responses and protection from tumor challenge in two different breast cancer models. Further incorporation of the immunostimulatory molecules IL-12 and B7-1 onto the PMVs by protein transfer enhanced tumor protection and induced beneficial Th1 and Th2-type HER-2-specific immune responses. Since protein antigens can be easily converted to GPI-anchored forms, these results demonstrate that isolated plasma membrane vesicles can be modified with desired antigens along with immunostimulatory molecules by protein transfer and used as a vaccine delivery vehicle to elicit potent antigen-specific immunity.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jaina M
authors.initials: JM
authors.lastname: Patel
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Vincent F
authors.initials: VF
authors.lastname: Vartabedian
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Erica N
authors.initials: EN
authors.lastname: Bozeman
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Brianne E
authors.initials: BE
authors.lastname: Caoyonan
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Srivatsan
authors.affiliation: Metaclipse Therapeutics Corporation, 3175 Presidential Drive, Atlanta, GA 30340, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pack
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Paulami
authors.initials: P
authors.lastname: Dey
authors.affiliation: Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: D'Souza
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Lily
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: pselvar@emory.edu.
authors.forename: Periasamy
authors.initials: P
authors.lastname: Selvaraj
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000941:Antigens / Q000737:chemistry*; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry; D006224:Cricetinae; D003412:Cricetulus; D006017:Glycolipids / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D006017:Glycolipids
keywords: Breast cancer; Plasma membrane vesicle; Protein transfer; Tumor antigens; Vaccine