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J Control Release ; 220(Pt A): 329-340, 2015 Dec 28.
Article in English | MEDLINE | ID: mdl-26522072

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.


Subject(s)
Brain Neoplasms/drug therapy , Cancer Vaccines/administration & dosage , Dextrans/administration & dosage , Drug Carriers , Glioma/drug therapy , HSP70 Heat-Shock Proteins/administration & dosage , Magnetite Nanoparticles/administration & dosage , Animals , Brain Neoplasms/immunology , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cancer Vaccines/chemistry , Cancer Vaccines/immunology , Cancer Vaccines/metabolism , Coculture Techniques , Dendritic Cells/drug effects , Dendritic Cells/immunology , Dendritic Cells/metabolism , Dextrans/chemistry , Dextrans/immunology , Dextrans/metabolism , Drug Compounding , Glioma/blood , Glioma/immunology , Glioma/metabolism , Glioma/pathology , 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 , Interferon-gamma/blood , K562 Cells , Lymphocytes, Tumor-Infiltrating/drug effects , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Magnetic Resonance Imaging , 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
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