title: 70-kDa heat shock protein coated magnetic nanocarriers as a nanovaccine for induction of anti-tumor immune response in experimental glioma.
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 (31)P 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.
authors.affiliation: Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, 194064 St. Petersburg, Russia; I.P. Pavlov State Medical University of St. Petersburg, Lev Tolstoy str. 6/8, 197022 St. Petersburg, Russia; A.L. Polenov Russian Research Scientific Institute of Neurosurgery, Mayakovsky str. 12, 191014 St. Petersburg, Russia; Technische Universität München, Klinikum rechts der Isar, Ismaniger Str. 22, 81675 Munich, Germany. Electronic address: shevtsov-max@mail.ru.
authors.forename: Maxim A
authors.initials: MA
authors.lastname: Shevtsov
authors.affiliation: Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, 191014 St. Petersburg, Russia.
authors.forename: Boris P
authors.initials: BP
authors.lastname: Nikolaev
authors.affiliation: Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, 191014 St. Petersburg, Russia.
authors.forename: Liudmila Y
authors.initials: LY
authors.lastname: Yakovleva
authors.affiliation: V.F. Fock Institute of Physics, St. Petersburg State University, Universitetskaya str. 7-9, 199034 St. Petersburg, Russia.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Parr
authors.affiliation: Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, 191014 St. Petersburg, Russia.
authors.forename: Yaroslav Y
authors.initials: YY
authors.lastname: Marchenko
authors.affiliation: Academic University of the Russian Academy of Sciences (RAS), Hlopina str. 8, 194021 St. Petersburg, Russia.
authors.forename: Igor
authors.initials: I
authors.lastname: Eliseev
authors.affiliation: Academic University of the Russian Academy of Sciences (RAS), Hlopina str. 8, 194021 St. Petersburg, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Yudenko
authors.affiliation: Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), Bolshoi pr. 31, 199004 St. Petersburg, Russia.
authors.forename: Anatolii V
authors.initials: AV
authors.lastname: Dobrodumov
authors.affiliation: Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, 191014 St. Petersburg, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Zlobina
authors.affiliation: Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, 191014 St. Petersburg, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zhakhov
authors.affiliation: Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, 191014 St. Petersburg, Russia.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Ischenko
authors.affiliation: The Wharton School, University of Pennsylvania, 3730 Walnut St., Philadelphia, PA 19104, USA.
authors.forename: Emil
authors.initials: E
authors.lastname: Pitkin
authors.affiliation: Technische Universität München, Klinikum rechts der Isar, Ismaniger Str. 22, 81675 Munich, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Multhoff
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003911:Dextrans / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D005910:Glioma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007114:Immunization; D007371:Interferon-gamma / Q000097:blood; D020014:K562 Cells; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D050997:Nanomedicine; D054730:Protein Interaction Domains and Motifs; D066244:Proton Magnetic Resonance Spectroscopy; D017208:Rats, Wistar; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D019496:Cancer Vaccines; D003911:Dextrans; D004337:Drug Carriers; D018840:HSP70 Heat-Shock Proteins; D058185:Magnetite Nanoparticles; D007371:Interferon-gamma; C065507:ferumoxides
keywords: Brain tumor; Hsp70; Immunotherapy; Magnetic nanoparticles; Vaccine