PMID- 26461116 OWN - NLM STAT- MEDLINE DCOM- 20161019 LR - 20181113 IS - 1878-5905 (Electronic) IS - 0142-9612 (Print) IS - 0142-9612 (Linking) VI - 74 DP - 2016 Jan TI - Plasma membrane vesicles decorated with glycolipid-anchored antigens and adjuvants via protein transfer as an antigen delivery platform for inhibition of tumor growth. PG - 231-44 LID - S0142-9612(15)00782-6 [pii] LID - 10.1016/j.biomaterials.2015.09.031 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Patel, Jaina M AU - Patel JM AD - Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Vartabedian, Vincent F AU - Vartabedian VF AD - Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Bozeman, Erica N AU - Bozeman EN AD - Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Caoyonan, Brianne E AU - Caoyonan BE AD - Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Srivatsan, Sanjay AU - Srivatsan S AD - Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Pack, Christopher D AU - Pack CD AD - Metaclipse Therapeutics Corporation, 3175 Presidential Drive, Atlanta, GA 30340, USA. FAU - Dey, Paulami AU - Dey P AD - Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - D'Souza, Martin J AU - D'Souza MJ AD - Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA. FAU - Yang, Lily AU - Yang L AD - Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Selvaraj, Periasamy AU - Selvaraj P AD - Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: pselvar@emory.edu. LA - eng GR - F31 CA165632/CA/NCI NIH HHS/United States GR - R01 CA138993/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150928 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antigens) RN - 0 (Glycolipids) SB - IM MH - Adjuvants, Immunologic/*administration & dosage MH - Animals MH - Antigens/*chemistry MH - CHO Cells MH - Cell Membrane/chemistry MH - Cricetinae MH - Cricetulus MH - Glycolipids/*chemistry MH - Humans MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Neoplasms/immunology/pathology/*therapy PMC - PMC4661141 MID - NIHMS726473 OTO - NOTNLM OT - Breast cancer OT - Plasma membrane vesicle OT - Protein transfer OT - Tumor antigens OT - Vaccine COIS- Conflict of Interest: Dr. Selvaraj is a co-founder & equity holder of Metaclipse Therapeutics Corporation, which is a startup company formed to develop therapeutic cancer vaccines for humans using the protein transfer technology described here for which he is a co-inventor. Writing assistance was not utilized in the production of the manuscript. EDAT- 2015/10/16 06:00 MHDA- 2016/10/26 06:00 PMCR- 2017/01/01 CRDT- 2015/10/14 06:00 PHST- 2015/04/04 00:00 [received] PHST- 2015/09/19 00:00 [revised] PHST- 2015/09/23 00:00 [accepted] PHST- 2015/10/14 06:00 [entrez] PHST- 2015/10/16 06:00 [pubmed] PHST- 2016/10/26 06:00 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - S0142-9612(15)00782-6 [pii] AID - 10.1016/j.biomaterials.2015.09.031 [doi] PST - ppublish SO - Biomaterials. 2016 Jan;74:231-44. doi: 10.1016/j.biomaterials.2015.09.031. Epub 2015 Sep 28.