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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Veröffentlicht in:Journal of controlled release 2015-12, Vol.220 (Pt A), p.329-340
Hauptverfasser: 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
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container_end_page 340
container_issue Pt A
container_start_page 329
container_title Journal of controlled release
container_volume 220
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. [Display omitted]
doi_str_mv 10.1016/j.jconrel.2015.10.051
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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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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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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 &amp; 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 &amp; 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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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