Interestingly, TACI-deficient mice develop lymphomas, suggesting that TACI may be a negative regulator of B-cell activation and contribute to the proliferation of malignant cells [59]. BAFF can be Selleckchem BIBW2992 expressed by the tumour cell itself or by neighbouring cells

in the tumour microenvironment. Autocrine and paracrine production of BAFF have been detected in malignant cells, showing the protection of these cells from the spontaneous death. The studies also confirm that BAFF can augment tumour cell growth by either stimulating proliferation, inhibiting apoptosis or protecting malignant cells against drug-induced apoptosis. Hence, the blockade of BAFF and their receptors on malignant B cells can be a plausible therapeutic strategy in oncology [4, 57]. B-cell-directed therapies are promising new treatments for autoimmune disorders, especially rheumatoid arthritis and systemic lupus erythematosus [32, 60, 61]. Several BAFF blockers are in development, but mainly two types of BAFF antagonists have been tested in both animal and human

studies, one BAFF receptor-IgG fusion protein (Atacicept; TACI-Ig fusion protein) and one fully human IgG1 monoclonal antibody against BAFF (Belimumab). In patients with systemic lupus erythematosus, belimumab reduces total Selleck Palbociclib peripheral B cell numbers and immunoglobulin levels and improves disease activity by a reduction in the frequency of lupus flares [32, 62]. Initial studies with Atacicept showed both clinical efficacy and good tolerability when administered to patients with systemic lupus erythematosus and patients with rheumatoid arthritis. Treatment with Atacicept reduced the circulating levels of immunoglobulins and the number of peripheral B cells and trended to improve scores for disease activity of patients with rheumatoid arthritis [57]. However, further clinical studies are warranted [63, 64]. Two other new BAFF antagonists, BR3-Fc (BAFF receptor fusion protein) and A-623 (peptide fusion protein), have been developed and are currently in clinical trials [60].

In vitro, the treatment of CLL cells with a TACI-immunoglobulin fusion protein and neutralizing antibodies that were specific for BAFF decreased cell viability compared 4-Aminobutyrate aminotransferase with untreated cells. In addition, TACI-Ig treatment of mice infused with human CLL cells resulted in fewer circulating CLL cells than in mice that were treated with non-specific immunoglobulin. The results indicate that BAFF antagonists are potentially useful also in the treatment of B-cell malignancies [60, 65]. BAFF helps regulate and enhance both innate and adaptive immune responses. Significant clinical relevance and diagnostic potential of BAFF are suggested in systemic and organ-specific autoimmune disorders as well as in allergic, infectious and malignant diseases. Levels of BAFF in body fluids may indicate disease activity and be used to monitor disease course.