Anti-TNFRSF4 monoclonal antibody, clone 8E7

Aims: The present study aimed to compare the gene-expression profiling of CD133(+) and CD133(-) D10 cells. Materials & methods: Cancer stem cell-like properties and gene-expression profiling of CD133(+) D10 cells versus CD133(-) cells were evaluated. Results: The CD133(+) D10 cells showed significantly higher clonogenic and spheroid forming potential, also higher expression of stemness genes NANOG and OCT4A compared with the CD133(-) cells. Gene-expression profiling of CD133(+) versus CD133(-) D10 cells revealed that 130 genes including ABC transporter superfamily (ABCC1, ABCG2 and ABCC6) were upregulated, while 61 genes including apoptosis modifying genes (CASP8 and TNFRSF4) were downregulated. Conclusion: We conclude that many genes involved in drug resistance and tumor aggressiveness are upregulated in CD133(+) D10 cells and targeting them might be an efficient strategy for treatment of melanoma.

We performed a network-based analysis of DNA microarray data from allergen-challenged CD4(+) T cells from patients with seasonal allergic rhinitis. Differentially expressed genes were organized into a functionally annotated network using the Ingenuity Knowledge Database, which is based on manual review of more than 200 000 publications. The main function of this network is the regulation of lymphocyte apoptosis, a role associated with several genes of the tuber necrosis factor superfamily. The expression of TNFRSF4, one of the genes in this family, was found to be 48 times higher in allergen- challenged cells than in diluent-challenged cells. TNFRSF4 is known to inhibit apoptosis and to enhance Th2 proliferation. Examination of a different material of allergen- stimulated peripheral blood mononuclear cells showed a higher number of interleukin-4(+) type 2 CD4(+) T (Th2) cells in patients than in controls (P < 0.01), as well as a higher number of non-apoptotic Th2 cells in patients (P < 0.01). The number of Th2 cells expressing TNFRSF4, TNFSF7 and TNFRSF1B was also significantly higher in patients. Treatment with anti-TNFSF4 resulted in a significantly decreased number of Th2 cells (P < 0.05). A logical inference from all this is that the proliferation of allergen-challenged Th2 cells is associated with a decreased apoptosis of Th2 cells and an increase in TNFRSF4 signalling.