70-kDa heat shock protein coated magnetic nanocarriers as a nanovaccine for induction of anti-tumor immune response in experimental glioma
Nanovaccines based on superparamagnetic iron oxide nanoparticles (SPIONs) provide a novel approach to induce the humoral and cell-based immune system to fight cancer. Herein, we increased the immunostimulatory capacity of SPIONs by coating them with recombinant heat shock protein 70 (Hsp70) which is...
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creator | Shevtsov, Maxim A. Nikolaev, Boris P. Yakovleva, Liudmila Y. Parr, Marina A. Marchenko, Yaroslav Y. Eliseev, Igor Yudenko, Anna Dobrodumov, Anatolii V. Zlobina, Olga Zhakhov, Alexander Ischenko, Alexander M. Pitkin, Emil Multhoff, Gabriele |
description | Nanovaccines based on superparamagnetic iron oxide nanoparticles (SPIONs) provide a novel approach to induce the humoral and cell-based immune system to fight cancer. Herein, we increased the immunostimulatory capacity of SPIONs by coating them with recombinant heat shock protein 70 (Hsp70) which is known to chaperone antigenic peptides. After binding, Hsp70–SPIONs deliver immunogenic peptides from tumor lysates to dendritiс cells (DCs) and thus stimulate a tumor-specific, CD8+ cytotoxic T cell response. We could show that binding activity of Hsp70–SPIONs to the substrate-binding domain (SBD) is highly dependent on the ATPase activity of its nucleotide-binding domain NBD), as shown by 31P NMR spectroscopy. Immunization of C6 glioma-bearing rats with DCs pulsed with Hsp70–SPIONs and tumor lysates resulted in a delayed tumor progression (as measured by MRI) and an increased overall survival. In parallel an increased IFNγ secretion were detected in the serum of these animals and immunohistological analysis of subsequent cryosections of the glioma revealed an enhanced infiltration of memory CD45RO+ and cytotoxic CD8+ T cells. Taken together the study demonstrates that magnetic nanocarriers such as SPIONs coated with Hsp70 can be applied as a platform for boosting anti-cancer immune responses.
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doi_str_mv | 10.1016/j.jconrel.2015.10.051 |
format | Article |
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[Display omitted]</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2015.10.051</identifier><identifier>PMID: 26522072</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Brain Neoplasms - drug therapy ; Brain Neoplasms - immunology ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Brain tumor ; Cancer Vaccines - administration & dosage ; Cancer Vaccines - chemistry ; Cancer Vaccines - immunology ; Cancer Vaccines - metabolism ; Coculture Techniques ; Dendritic Cells - drug effects ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Dextrans - administration & dosage ; Dextrans - chemistry ; Dextrans - immunology ; Dextrans - metabolism ; Drug Carriers ; Drug Compounding ; Glioma - blood ; Glioma - drug therapy ; Glioma - immunology ; Glioma - metabolism ; Glioma - pathology ; Hsp70 ; HSP70 Heat-Shock Proteins - administration & dosage ; HSP70 Heat-Shock Proteins - chemistry ; HSP70 Heat-Shock Proteins - immunology ; HSP70 Heat-Shock Proteins - metabolism ; Humans ; Immunity, Cellular - drug effects ; Immunity, Humoral - drug effects ; Immunization ; Immunotherapy ; Interferon-gamma - blood ; K562 Cells ; Lymphocytes, Tumor-Infiltrating - drug effects ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - metabolism ; Magnetic nanoparticles ; Magnetic Resonance Imaging ; Magnetite Nanoparticles - administration & dosage ; Magnetite Nanoparticles - chemistry ; Male ; Melanoma, Experimental ; Mice ; Nanomedicine ; Protein Interaction Domains and Motifs ; Proton Magnetic Resonance Spectroscopy ; Rats, Wistar ; T-Lymphocytes, Cytotoxic - drug effects ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Cytotoxic - metabolism ; Time Factors ; Tumor Burden - drug effects ; Vaccine</subject><ispartof>Journal of controlled release, 2015-12, Vol.220 (Pt A), p.329-340</ispartof><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-546d11b2f224f09b0044238e8041c72cc5662ed63a7de99213306c3d333d3693</citedby><cites>FETCH-LOGICAL-c468t-546d11b2f224f09b0044238e8041c72cc5662ed63a7de99213306c3d333d3693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0168365915302170$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26522072$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shevtsov, Maxim A.</creatorcontrib><creatorcontrib>Nikolaev, Boris P.</creatorcontrib><creatorcontrib>Yakovleva, Liudmila Y.</creatorcontrib><creatorcontrib>Parr, Marina A.</creatorcontrib><creatorcontrib>Marchenko, Yaroslav Y.</creatorcontrib><creatorcontrib>Eliseev, Igor</creatorcontrib><creatorcontrib>Yudenko, Anna</creatorcontrib><creatorcontrib>Dobrodumov, Anatolii V.</creatorcontrib><creatorcontrib>Zlobina, Olga</creatorcontrib><creatorcontrib>Zhakhov, Alexander</creatorcontrib><creatorcontrib>Ischenko, Alexander M.</creatorcontrib><creatorcontrib>Pitkin, Emil</creatorcontrib><creatorcontrib>Multhoff, Gabriele</creatorcontrib><title>70-kDa heat shock protein coated magnetic nanocarriers as a nanovaccine for induction of anti-tumor immune response in experimental glioma</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>Nanovaccines based on superparamagnetic iron oxide nanoparticles (SPIONs) provide a novel approach to induce the humoral and cell-based immune system to fight cancer. Herein, we increased the immunostimulatory capacity of SPIONs by coating them with recombinant heat shock protein 70 (Hsp70) which is known to chaperone antigenic peptides. After binding, Hsp70–SPIONs deliver immunogenic peptides from tumor lysates to dendritiс cells (DCs) and thus stimulate a tumor-specific, CD8+ cytotoxic T cell response. We could show that binding activity of Hsp70–SPIONs to the substrate-binding domain (SBD) is highly dependent on the ATPase activity of its nucleotide-binding domain NBD), as shown by 31P NMR spectroscopy. Immunization of C6 glioma-bearing rats with DCs pulsed with Hsp70–SPIONs and tumor lysates resulted in a delayed tumor progression (as measured by MRI) and an increased overall survival. In parallel an increased IFNγ secretion were detected in the serum of these animals and immunohistological analysis of subsequent cryosections of the glioma revealed an enhanced infiltration of memory CD45RO+ and cytotoxic CD8+ T cells. Taken together the study demonstrates that magnetic nanocarriers such as SPIONs coated with Hsp70 can be applied as a platform for boosting anti-cancer immune responses.
[Display omitted]</description><subject>Animals</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - immunology</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain tumor</subject><subject>Cancer Vaccines - administration & dosage</subject><subject>Cancer Vaccines - chemistry</subject><subject>Cancer Vaccines - immunology</subject><subject>Cancer Vaccines - metabolism</subject><subject>Coculture Techniques</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Dextrans - administration & dosage</subject><subject>Dextrans - chemistry</subject><subject>Dextrans - immunology</subject><subject>Dextrans - metabolism</subject><subject>Drug Carriers</subject><subject>Drug Compounding</subject><subject>Glioma - blood</subject><subject>Glioma - drug therapy</subject><subject>Glioma - immunology</subject><subject>Glioma - metabolism</subject><subject>Glioma - pathology</subject><subject>Hsp70</subject><subject>HSP70 Heat-Shock Proteins - administration & dosage</subject><subject>HSP70 Heat-Shock Proteins - chemistry</subject><subject>HSP70 Heat-Shock Proteins - immunology</subject><subject>HSP70 Heat-Shock Proteins - metabolism</subject><subject>Humans</subject><subject>Immunity, Cellular - drug effects</subject><subject>Immunity, Humoral - drug effects</subject><subject>Immunization</subject><subject>Immunotherapy</subject><subject>Interferon-gamma - blood</subject><subject>K562 Cells</subject><subject>Lymphocytes, Tumor-Infiltrating - drug effects</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - metabolism</subject><subject>Magnetic nanoparticles</subject><subject>Magnetic Resonance Imaging</subject><subject>Magnetite Nanoparticles - administration & dosage</subject><subject>Magnetite Nanoparticles - chemistry</subject><subject>Male</subject><subject>Melanoma, Experimental</subject><subject>Mice</subject><subject>Nanomedicine</subject><subject>Protein Interaction Domains and Motifs</subject><subject>Proton Magnetic Resonance Spectroscopy</subject><subject>Rats, Wistar</subject><subject>T-Lymphocytes, Cytotoxic - drug effects</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Cytotoxic - metabolism</subject><subject>Time Factors</subject><subject>Tumor Burden - drug effects</subject><subject>Vaccine</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1rHDEMhk1JabZpf0KLj7nM1h9jz8wphKRfEOgld-OVNYk3M_bG9oT2L_RX19vd5BqQEbw8kiy9hHzibM0Z11-26y3EkHBaC8ZV1dZM8TdkxftONu0wqBOyqlzfSK2GU_I-5y1jTMm2e0dOhVZCsE6syN-ONQ_Xlt6jLTTfR3iguxQL-kAh2oKOzvYuYPFAgw0RbEoeU6a2xn_lyQL4gHSMifrgFig-BhpHakPxTVnmvT7PS0US5l0MGStH8fcOk58xFDvRu8nH2X4gb0c7Zfx4zGfk9tvX26sfzc2v7z-vLm8aaHVfGtVqx_lGjEK0Ixs2jLWtkD32rOXQCQCltUCnpe0cDoPgUjIN0klZnx7kGTk_tK17Pi6Yi5l9BpwmGzAu2fBOcT6o2qWi6oBCijknHM2u_tmmP4Yzs3fBbM3RBbN3YS9XF2rd5-OIZTOje6l6PnsFLg4A1j2f6kFNBo8B0PmEUIyL_pUR_wCoG5yV</recordid><startdate>20151228</startdate><enddate>20151228</enddate><creator>Shevtsov, Maxim A.</creator><creator>Nikolaev, Boris P.</creator><creator>Yakovleva, Liudmila Y.</creator><creator>Parr, Marina A.</creator><creator>Marchenko, Yaroslav Y.</creator><creator>Eliseev, Igor</creator><creator>Yudenko, Anna</creator><creator>Dobrodumov, Anatolii V.</creator><creator>Zlobina, Olga</creator><creator>Zhakhov, Alexander</creator><creator>Ischenko, Alexander M.</creator><creator>Pitkin, Emil</creator><creator>Multhoff, Gabriele</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20151228</creationdate><title>70-kDa heat shock protein coated magnetic nanocarriers as a nanovaccine for induction of anti-tumor immune response in experimental glioma</title><author>Shevtsov, Maxim A. ; Nikolaev, Boris P. ; Yakovleva, Liudmila Y. ; Parr, Marina A. ; Marchenko, Yaroslav Y. ; Eliseev, Igor ; Yudenko, Anna ; Dobrodumov, Anatolii V. ; Zlobina, Olga ; Zhakhov, Alexander ; Ischenko, Alexander M. ; Pitkin, Emil ; Multhoff, Gabriele</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-546d11b2f224f09b0044238e8041c72cc5662ed63a7de99213306c3d333d3693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Brain Neoplasms - immunology</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain Neoplasms - pathology</topic><topic>Brain tumor</topic><topic>Cancer Vaccines - administration & dosage</topic><topic>Cancer Vaccines - chemistry</topic><topic>Cancer Vaccines - immunology</topic><topic>Cancer Vaccines - metabolism</topic><topic>Coculture Techniques</topic><topic>Dendritic Cells - drug effects</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Dextrans - administration & dosage</topic><topic>Dextrans - chemistry</topic><topic>Dextrans - immunology</topic><topic>Dextrans - metabolism</topic><topic>Drug Carriers</topic><topic>Drug Compounding</topic><topic>Glioma - blood</topic><topic>Glioma - drug therapy</topic><topic>Glioma - immunology</topic><topic>Glioma - metabolism</topic><topic>Glioma - pathology</topic><topic>Hsp70</topic><topic>HSP70 Heat-Shock Proteins - administration & dosage</topic><topic>HSP70 Heat-Shock Proteins - chemistry</topic><topic>HSP70 Heat-Shock Proteins - immunology</topic><topic>HSP70 Heat-Shock Proteins - metabolism</topic><topic>Humans</topic><topic>Immunity, Cellular - drug effects</topic><topic>Immunity, Humoral - drug effects</topic><topic>Immunization</topic><topic>Immunotherapy</topic><topic>Interferon-gamma - blood</topic><topic>K562 Cells</topic><topic>Lymphocytes, Tumor-Infiltrating - drug effects</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - metabolism</topic><topic>Magnetic nanoparticles</topic><topic>Magnetic Resonance Imaging</topic><topic>Magnetite Nanoparticles - administration & dosage</topic><topic>Magnetite Nanoparticles - chemistry</topic><topic>Male</topic><topic>Melanoma, Experimental</topic><topic>Mice</topic><topic>Nanomedicine</topic><topic>Protein Interaction Domains and Motifs</topic><topic>Proton Magnetic Resonance Spectroscopy</topic><topic>Rats, Wistar</topic><topic>T-Lymphocytes, Cytotoxic - drug effects</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>T-Lymphocytes, Cytotoxic - metabolism</topic><topic>Time Factors</topic><topic>Tumor Burden - drug effects</topic><topic>Vaccine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shevtsov, Maxim A.</creatorcontrib><creatorcontrib>Nikolaev, Boris P.</creatorcontrib><creatorcontrib>Yakovleva, Liudmila Y.</creatorcontrib><creatorcontrib>Parr, Marina A.</creatorcontrib><creatorcontrib>Marchenko, Yaroslav Y.</creatorcontrib><creatorcontrib>Eliseev, Igor</creatorcontrib><creatorcontrib>Yudenko, Anna</creatorcontrib><creatorcontrib>Dobrodumov, Anatolii V.</creatorcontrib><creatorcontrib>Zlobina, Olga</creatorcontrib><creatorcontrib>Zhakhov, Alexander</creatorcontrib><creatorcontrib>Ischenko, Alexander M.</creatorcontrib><creatorcontrib>Pitkin, Emil</creatorcontrib><creatorcontrib>Multhoff, Gabriele</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shevtsov, Maxim A.</au><au>Nikolaev, Boris P.</au><au>Yakovleva, Liudmila Y.</au><au>Parr, Marina A.</au><au>Marchenko, Yaroslav Y.</au><au>Eliseev, Igor</au><au>Yudenko, Anna</au><au>Dobrodumov, Anatolii V.</au><au>Zlobina, Olga</au><au>Zhakhov, Alexander</au><au>Ischenko, Alexander M.</au><au>Pitkin, Emil</au><au>Multhoff, Gabriele</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>70-kDa heat shock protein coated magnetic nanocarriers as a nanovaccine for induction of anti-tumor immune response in experimental glioma</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2015-12-28</date><risdate>2015</risdate><volume>220</volume><issue>Pt A</issue><spage>329</spage><epage>340</epage><pages>329-340</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><abstract>Nanovaccines based on superparamagnetic iron oxide nanoparticles (SPIONs) provide a novel approach to induce the humoral and cell-based immune system to fight cancer. Herein, we increased the immunostimulatory capacity of SPIONs by coating them with recombinant heat shock protein 70 (Hsp70) which is known to chaperone antigenic peptides. After binding, Hsp70–SPIONs deliver immunogenic peptides from tumor lysates to dendritiс cells (DCs) and thus stimulate a tumor-specific, CD8+ cytotoxic T cell response. We could show that binding activity of Hsp70–SPIONs to the substrate-binding domain (SBD) is highly dependent on the ATPase activity of its nucleotide-binding domain NBD), as shown by 31P NMR spectroscopy. Immunization of C6 glioma-bearing rats with DCs pulsed with Hsp70–SPIONs and tumor lysates resulted in a delayed tumor progression (as measured by MRI) and an increased overall survival. In parallel an increased IFNγ secretion were detected in the serum of these animals and immunohistological analysis of subsequent cryosections of the glioma revealed an enhanced infiltration of memory CD45RO+ and cytotoxic CD8+ T cells. Taken together the study demonstrates that magnetic nanocarriers such as SPIONs coated with Hsp70 can be applied as a platform for boosting anti-cancer immune responses.
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subjects | Animals Brain Neoplasms - drug therapy Brain Neoplasms - immunology Brain Neoplasms - metabolism Brain Neoplasms - pathology Brain tumor Cancer Vaccines - administration & dosage Cancer Vaccines - chemistry Cancer Vaccines - immunology Cancer Vaccines - metabolism Coculture Techniques Dendritic Cells - drug effects Dendritic Cells - immunology Dendritic Cells - metabolism Dextrans - administration & dosage Dextrans - chemistry Dextrans - immunology Dextrans - metabolism Drug Carriers Drug Compounding Glioma - blood Glioma - drug therapy Glioma - immunology Glioma - metabolism Glioma - pathology Hsp70 HSP70 Heat-Shock Proteins - administration & dosage HSP70 Heat-Shock Proteins - chemistry HSP70 Heat-Shock Proteins - immunology HSP70 Heat-Shock Proteins - metabolism Humans Immunity, Cellular - drug effects Immunity, Humoral - drug effects Immunization Immunotherapy Interferon-gamma - blood K562 Cells Lymphocytes, Tumor-Infiltrating - drug effects Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism Magnetic nanoparticles Magnetic Resonance Imaging Magnetite Nanoparticles - administration & dosage Magnetite Nanoparticles - chemistry Male Melanoma, Experimental Mice Nanomedicine Protein Interaction Domains and Motifs Proton Magnetic Resonance Spectroscopy Rats, Wistar T-Lymphocytes, Cytotoxic - drug effects T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - metabolism Time Factors Tumor Burden - drug effects Vaccine |
title | 70-kDa heat shock protein coated magnetic nanocarriers as a nanovaccine for induction of anti-tumor immune response in experimental glioma |
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