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 tha...

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Bibliographic Details
Published in:Biomaterials 2016-01, Vol.74, p.231-244
Main Authors: Patel, Jaina M, Vartabedian, Vincent F, Bozeman, Erica N, Caoyonan, Brianne E, Srivatsan, Sanjay, Pack, Christopher D, Dey, Paulami, D'Souza, Martin J, Yang, Lily, Selvaraj, Periasamy
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - administration & dosage
Advanced Basic Science
Animals
Antigens
Antigens - chemistry
Breast
Breast cancer
Cancer
Cell Membrane - chemistry
CHO Cells
Cricetinae
Cricetulus
Dentistry
Glycolipids - chemistry
Humans
Immunity
Membranes
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neoplasms - immunology
Neoplasms - pathology
Neoplasms - therapy
Plasma membrane vesicle
Protein transfer
Proteins
Tumor antigens
Tumors
Vaccine
Vesicles
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2015.09.031