title: Influenza virus-like particles engineered by protein transfer with tumor-associated antigens induces protective antitumor immunity.
abstract: Delivery of antigen in particulate form using either synthetic or natural particles induces stronger immunity than soluble forms of the antigen. Among naturally occurring particles, virus-like particles (VLPs) have been genetically engineered to express tumor-associated antigens (TAAs) and have shown to induce strong TAA-specific immune responses due to their nano-particulate size and ability to bind and activate antigen-presenting cells. In this report, we demonstrate that influenza VLPs can be modified by a protein transfer technology to express TAAs for induction of effective antitumor immune responses. We converted the breast cancer HER-2 antigen to a glycosylphosphatidylinositol (GPI)-anchored form and incorporated GPI-HER-2 onto VLPs by a rapid protein transfer process. Expression levels on VLPs depended on the GPI-HER-2 concentration added during protein transfer. Vaccination of mice with protein transferred GPI-HER-2-VLPs induced a strong Th1 and Th2-type anti-HER-2 antibody response and protected mice against a HER-2-expressing tumor challenge. The Soluble form of GPI-HER-2 induced only a weak Th2 response under similar conditions. These results suggest that influenza VLPs can be enriched with TAAs by protein transfer to develop effective VLP-based subunit vaccines against cancer without chemical or genetic modifications and thus preserve the immune stimulating properties of VLPs for easier production of antigen-specific therapeutic cancer vaccines.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, 30322, Georgia.
authors.forename: Jaina M
authors.initials: JM
authors.lastname: Patel
authors.forename: Vincent F
authors.initials: VF
authors.lastname: Vartabedian
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Kim
authors.forename: Sara
authors.initials: S
authors.lastname: He
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
authors.forename: Periasamy
authors.initials: P
authors.lastname: Selvaraj
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D006801:Humans; D007109:Immunity; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control*; D009975:Orthomyxoviridae / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004337:Drug Carriers; D018719:Erb-b2 Receptor Tyrosine Kinases; D058425:Vaccines, Virus-Like Particle; C508053:ERBB2 protein, human
keywords: HER-2; breast cancer; protein transfer; vaccine; virus-like particles