Effective immunotherapy of rat glioblastoma with prolonged intratumoral delivery of exogenous heat shock protein Hsp70

International Journal of Cancer - Tập 135 Số 9 - Trang 2118-2128 - 2014
Maxim Shevtsov1, A. V. Pozdnyakov2, А. Л. Михрина3, B. P. Nikolaev4, А. В. Добродумов5, Elena Y. Komarova1, Darya A. Meshalkina1, A. Ischenko6, Emil Pitkin7, Irina V. Guzhova1, Т. Д. Власов1
1Laboratory of Cell Protection Mechanisms, Institute of Cytology of the Russian Academy of Sciences (RAS), St. Petersburg, Russia
2Department of Radiology, City Clinical Oncology Dispenser, St. Petersburg, Russia
3Department of Morphology, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg, Russia
4Laboratory of Medical Nanotechnology, Research Institute of Highly Pure Biopreparations, St. Petersburg, Russia
5NMR Laboratory, Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), St. Petersburg, Russia
6Department of protein biochemistry, Research Institute of Highly Pure Biopreparations, St. Petersburg, Russia
7Wharton School, University of Pennsylvania, Philadelphia, Pa.

Tóm tắt

Chaperone Hsp70 can activate adaptive immunity suggesting its possible application as an antitumor vaccine. To assess the therapeutic capacity of Hsp70 we administered purified chaperone into a C6 glioblastoma brain tumor and explored the viability and tumor size as well as interferon gamma (IFNγ) production and cytotoxicity of lymphocytes in the treated animals. Targeted intratumoral injection of Hsp70 resulted in its distribution within the area of glioblastoma, and caused significant inhibition of tumor progression as confirmed by magnetic resonance imaging. The delay in tumor growth corresponded to the prolonged survival of tumor‐bearing animals of up to 31 days versus 20 days in control. Continuous administration of Hsp70 with an osmotic pump increased survival even further (39 days). Therapeutic efficacy was associated with infiltration to glioblastoma of NK cells (Ly‐6c+) and T lymphocytes (CD3+, CD4+ and CD8+) as well as with an increase in the activity of NK cells (granzyme B production) and CD8+ T lymphocytes as shown by IFNγ ELISPOT assay. Furthermore, we found that Hsp70 treatment caused concomitantly, with a tenfold elevated IFNγ production, an increase in anti‐C6 tumor cytotoxicity of lymphocytes. In conclusion, continuous intratumoral delivery of Hsp70 demonstrates high therapeutic potential and therefore could be applied in the treatment of glioblastoma.

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Thông tin xuất bản

International Journal of Cancer

Tập 135 Số 9

2118-2128

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