70-KDA HEAT SHOCK PROTEIN COATED MAGNETIC NANOCARRIERS AS A NANOVACCINE FOR INDUCTION OF ANTI-TUMOR IMMUNE RESPONSE IN EXPERIMENTAL GLIOMA
MaximA. Shevtsov, Boris P. Nikolaev, Liudmila Y. Yakovleva, Marina A. Parr, Yaroslav Y. Marchenko, Igor Eliseev, Anatolii V. Dobrodumov, Olga Zlobina, Alexander Zhakhov, Alexander M. Ischenko, Emil Pitkin, Gabriele Multhoff. (29-10-2015).Elsevier B.V., 2015, doi.org/10.1016/j.jconrel.2015.10.05
Research Area B
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 themwith 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 pulsedwith Hsp70–SPIONs and tumor lysates resulted in a delayed tumor progression (as measured byMRI) 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.