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 (IFNc) 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-6c1) and T lymphocytes (CD31, CD41 and CD81) as well as with an increase in the activity of NK cells (granzyme B production) and CD81 T lymphocytes as shown by IFNc ELISPOT assay. Furthermore, we found that Hsp70 treatment caused concomitantly, with a tenfold elevated IFNc 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.Multiform glioblastoma is the most aggressive and common primary brain tumor in adults 1 with an incidence rate of 7.3 cases per 100,000 persons per year.2 The standard treatment for newly diagnosed glioblastoma currently includes surgical resection followed by radiotherapy and chemotherapy using apoptosis-inducing factors such as temozolomide, which is actively used nowadays. 3During the last two decades, increasing evidence has demonstrated that the high immunomodulatory potency of heat shock protein 70 (Hsp70) is due to its ability to specifically bind tumor antigens and present them to dendritic antigenpresenting cells (APCs).4 Several anticancer and antivirus vaccines were created based on Hsp70 chaperone. First, immunization of mice bearing tumors with Hsp70-secreting murine ovarian cancer cells caused a strong anticancer effect concomitantly with the elicitation of CD41 and CD81 Tand NK-cell activity.5 Another chaperonic vaccine contains fusion products of Hsp70 with Herpes virus VP22 peptide (aa268-301) that facilitate intracellular transport; this construct was effective in inducing a specific cytotoxic response against mouse lymphoma cells.6 Third, Ito et al. showed that the combined intratumoral delivery of pure Hsp70 with heating magnetic particles can efficiently destroy mouse melanoma B16 in a therapeutic modality. 7 More recently, we reported that the application of purified Hsp70 onto skin area covering B16/F10 melanoma significantly inhibited tumor progression and increased the survival of animals. 8Although the mechanism of antitumor activity of Hsp70 remains unclear, it is believed that the chaperone can trigger both innate and ...

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A total of 65 patients with clinically significant diagnoses of remitting multiple sclerosis in the stage of remission were studied. Neurological status was investigated with assessment on the FS and EDSS scales, with neuropsychological testing, and MRI scans (1.5 T). The severity of brain atrophy (in terms of the parenchyma volume) and the total volume of foci on T2 images were assessed as proportions of intracerebral volume. The severity of neurological deficit depended on the volume of intratentorial focal lesions and the level of brain atrophy. Cognitive disorders were identified in 89% of patients, and the severity of these was associated with the level of atrophy and the volume of foci on T2 images in the dominant hemisphere.

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