Influenza virus-like particles engineered by protein transfer with tumor-associated antigens induces protective antitumor immunity.
Biotechnol Bioeng
; 112(6): 1102-10, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25689082
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Orthomyxoviridae
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Portadores de Fármacos
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Receptor ErbB-2
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Vacinas Anticâncer
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Vacinas de Partículas Semelhantes a Vírus
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Antígenos de Neoplasias
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Neoplasias
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article