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 | Jaina M Patel, Vincent F Vartabedian, Min-Chul Kim, Sara He, Sang-Moo Kang, Periasamy Selvaraj |
Journal | Biotechnology and bioengineering
(Biotechnol Bioeng)
Vol. 112
Issue 6
Pg. 1102-10
(Jun 2015)
ISSN: 1097-0290 [Electronic] United States |
PMID | 25689082
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Copyright | © 2015 Wiley Periodicals, Inc. |
Chemical References |
- Antibodies, Neoplasm
- Antigens, Neoplasm
- Cancer Vaccines
- Drug Carriers
- Vaccines, Virus-Like Particle
- ERBB2 protein, human
- Receptor, ErbB-2
|
Topics |
- Animals
- Antibodies, Neoplasm
(blood)
- Antigens, Neoplasm
(genetics, immunology, metabolism)
- Cancer Vaccines
(administration & dosage, genetics, immunology)
- Disease Models, Animal
- Drug Carriers
- Humans
- Immunity
- Mice
- Neoplasms
(immunology, prevention & control)
- Orthomyxoviridae
(genetics, metabolism)
- Receptor, ErbB-2
(genetics, immunology, metabolism)
- Vaccines, Virus-Like Particle
(administration & dosage, genetics, immunology)
|