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The review is devoted to a relatively young direction in therapy of malignant gliomas, which is based on applying monoclonal antibodies against tumour-associated antigens. The current data on efficacy of main therapeutic agents in clinical practice or clinical trials concerning high-grade gliomas, especially glioblastoma multiforme, is summarized. Of particular interest is bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (anti-VEGF), which is widely used in glioblastoma. Major clinical trials devoted to bevacizumab monotherapy and combinations of bevacizumab with other therapeutic modalities in primary and recurrent glioblastoma conducted since 2006 till now are reviewed. The results ofexperimental and clinical application ofmonoclonal antibodies against epidermal growth factor receptor (EGFR) and its mutant variant EGFRvIII are analyzed, showing the most significant clinical effectiveness of nimotuzumab--a humanized monoclonal antibody. Significant part of the review is devoted to discussion of experimental and clinical data concerning efficacy of antibodies against VEGF receptor 2, platelet-derived growth factor receptor α, hepatocyte growth factor and its receptor c-Met. Unbiassed analysis of clinical trials on monoclonal antibodies does not allow us to conclude that passive immunotherapy directed against antigens listed above can significantly improve the overall survival of patients suffering from glioblastoma multiforme. This finding has encouraged us to mention several alternative approaches to passive immunotherapy and to list several prospective antigens for developing monoclonal antibodies.

Glioblastoma (GBM) is the most common type of primary brain cancer that characterized by poor prognosis due to the rapid progression, active angiogenesis, enhanced tumor cell invasion and the emergence of resistance toward conventional therapy. In this connection, nowadays, new approaches for selective inhibition of crucial steps in tumor progression are actively developing. The key feature of tumor growth and development is angiogenesis. VEGF and its receptor VEGFR2 play the pivotal role in regulation of tumor vessel formation. Therefore, VEGFR2, as the main receptor of VEGF's pro-angiogenic signal transducer, is a promising molecular target for anti-angiogenic therapy. There is evidence that inhibitors of VEGF and VEGFR2 reduce endothelial cell proliferation, migration and survival that lead to regression of vessel density and decrease vascular permeability, thereby slowing tumor growth. Currently, a number of VEGFR2 inhibitors are under clinical trials (ramucirumab, cediranib) and several were approved (sunitinib, sorafenib). Despite the promising results of preclinical studies, the efficacy of antiangiogenic drugs in the clinical practice is significantly lower, mainly, due to rapid adaptation of malignant cells that consists of alternative pro-angiogenic pathways activation, recruitment of endothelial progenitor cells from bone marrow and increasing of the invasive growth. Given the diversity of pro-angiogenic mechanisms, enhancement of the efficacy of tumor therapy could be achieved by specific inhibition of VEGFR2 functions that will be supplemented by other antiangiogenic drugs (anti-VEGF,-PIGF,-HIF1alpha). In addition, multitargeting therapy should focus on the combined inhibition of angiogenesis, invasion, metastasis, proliferation and survival of tumor cells.

The results of fundamental and applied studies of blood-brain barrier had been conducted by authors during the last 10 years are summarized in the publication. The molecular anatomy of barrier microvessels, as well as promising markers of BBB and other proteins involved in barrier functions are discussed. Via in vitro experiments with endothelial cells of cerebral microvessels we characterized the basic conditions required for adequate BBB modeling. The in vivo data of BBB permeability for macromolecules in normal and different pathological process is including radiation injury, hyperosmotic shock, and nervous tissue ischemia are properly described. A particular attention was focused upon the experimental studies of the permeability and functional reorganization of barrier endothelium during tumor neoangiogenesis. We detected a dramatically increased permeability of neoplastic microvessels both for horseradish peroxidase/serum albumin and labeled monoclonal antibodies. The increased tumor permeability for IgG and the overexpression of target antigens in tumor tissue and peritumoral zone make possible the targeted delivery of diagnostics and therapeutic agents into the tumor by means of monoclonal antibodies.

Solid tumor progression largely depends on vascularization and angiogenesis in the malignant tissue. The most prominent among all proangiogenic factors is vascular endothelium growth factor (VEGF). VEGF suppression leads to retrogression of neoplastic vessels and tumor growth restriction. Clinical trials of complex antiangiogenic and chemical therapy of different neoplastic tumors have shown promising results. Nowadays bevacizumab is widely used in breast cancer, colorectal cancer and II-IV stage of malignancy gliomas treatment. Unfortunately, in the majority of cases antiangiogenic treatment led not to full recovery, but only to tumor development restriction. Resistance mechanisms include potentiating of alternative proangiogenic signaling pathways and activation of malignant cell invasive population.

Appearance of neurospecific proteins (NSP) outside the brain plays a certain pathogenetic role in the development of autosensitization occurring in many kinds of CNS injuries and diseases. Analysis of modern views of cerebrospinal fluid (CSF) exchange allows us to suppose that NSP are eliminated from the brain tissue within CSF, moving from the subarachnoid space into cranial veins, and by lymphatic way, into deep cervical lymph nodes. Elevation of NSP level in CSF indicates an actual neudegenerative process. Serum levels of NSP are determined by the balance between the elimination of NSP from the brain, on the one hand, and their metabolism and the response of the immune system to the appearance of these autoantigenes in the blood stream, on the other. Basing on their own data on the dynamics of NSP (NSE, GFAR, and MBP) concentrations and the proportions of these proteins in CSF and serum (coefficient of elimination) in rats after ischemic, hypoxic, and autoimmune cerebral lesions, the authors offer an algorithm of pathogenetic evaluation, including, on the one part, a conclusion on the presence or absence of a neurodegenerative process, and, on the other, a conclusion on a normal or lowered rate of NSP elimination (metabolism). The results of such an analysis may have a clinical significance in terms of the development of a pathogenetic therapy, including, in every individual case, not only neuroprotectors, but also pharmaceuticals directed towards correction of the functional condition of the immune system.

Immunochemical monitoring was used to examine 37 patients with remittent multiple sclerosis (MS) for 3 years. There were changes in the blood concentrations of the supernatants IL-1 beta, IL-2, IL-6, alpha-TNF, in the serum levels of the adhesion molecule sVCAM, the neurospecific proteins GFAP and alpha 2GP. Only does active MS show a simultaneous increase in the serum concentrations of SVCAM and GFAP and alpha 2GP, which may be used as a test for the objectification of MS aggravation, the efficiency of therapy. The revealed higher secretion of antiinflammatory of cytokines at all disease stages, no recovery of blood-brain barrier responsiveness and at remission provide evidence for the likelihood of a permanent immunopathological process in MS with prevailing inflammatory and destructive changes during a clinical exacerbation and of the induction of active astrogliosis at its remission.