Plasma membrane vesicles decorated with glycolipid-anchored antigens and adjuvants via protein transfer as an antigen delivery platform for inhibition of tumor growth

• Type of Material: Article
• Authors: Jaina M. Patel, Emory University; Vincent F. Vartabedian, Emory University; Erica N. Bozeman, Emory University; Brianne E. Caoyonan, Emory University; Sanjay Srivatsan, Emory University; Christopher D. Pack, Metaclipse Therapeutics Corp; Paulami Dey, Emory University; Martin J. D'Souza, Mercer University; Lily Yang, Emory University; Periasamy Selvaraj, Emory University
• Language: English
• Date: 2016-01-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.biomaterials.2015.09.031
• Title of Journal or Parent Work: Biomaterials
• ISSN: 0142-9612
• Volume: 74
• Start Page: 231
• End Page: 244
• Grant/Funding Information: This work was supported in part by NIH grants R01 CA138993-01A1 (PS) and F31 CA165632-01 (JMP).
• Keywords: IN-VIVO; BREAST-CANCER; IL-12; Vaccine; CANCER-IMMUNOTHERAPY; PROTECTIVE ANTITUMOR IMMUNITY; Protein transfer; Materials Science; Breast cancer; GAMMA PRODUCTION; Plasma membrane vesicle; Tumor antigens; Science & Technology; TH2 CELLS; IMMUNOSTIMULATORY MOLECULES; Technology; VACCINE DELIVERY; Engineering; Engineering, Biomedical; Materials Science, Biomaterials; T-CELLS
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pathology

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.