[Monoclonal antibodies in high-grade gliomas].

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.

Expression of a recombinant extracellular fragment of human vascular endothelial growth factor receptor VEGFR1 in E. coli.

Human vascular endothelium growth factor receptor VEGFR1 is a type III fms-like tyrosine kinase with weakly pronounced tyrosine kinase function. The second and third IgG-like domains of the extracellular part of VEGFR1 act as "traps" for VEGF and are prospective candidates for antiangiogenic therapy of VEGF-dependent tumors. cDNA encoding extracellular Ig-like domains 2, 3, 4 of VEGFR1 was cloned in expressing vectors pET28a, pET32a, and pQE60. The recombinant protein was expressed in E. coli cells and purified by metal affinity chromatography. An expressing construction and a superproducer strain were created, allowing the production of high amounts of recombinant VEGFR1 extracellular fragment, needed for experimental in vivo antiangiogenic therapy.