Moreover, since S1P is a survival factor indispensable for the function of several vital tissues such as the immune and the cardiovascular system, targeted delivery and accumulation of StSPL specifically in diseased tissues might avoid side effects. This opens intriguing perspectives for S1P-targeted therapy using ligand-guided carrier systems. Recently, a molecular sponge approach has been described which is based on the use of a monoclonal antibody to absorb circulating S1P. Although conceptually similar to our approach, we believe that the use of antibodies for simple reversible absorption of S1P in extracellular tissues may less efficiently compete with the continuous release of S1P from various CPI-613 sources than irreversibly depleting the circulating S1P pool as StSPL does. Nevertheless, the reported results from in vitro and in vivo use of the antibody in tumor models are impressive and confirm the strategic advantage of specific S1P targeting compared to the use of available small molecules as S1P receptor antagonists. For example, the sphingosine analogue FTY720 has been commonly used as an immunosuppressive agent to treat autoimmune diseases based on the role of the S1P1 receptor in lymphocyte trafficking. The in vivo phosphorylated form of FTY720 initially acts as an S1P receptor agonist, but subsequently adopts an indirect antagonistic function by promoting receptor downmodulation and thus resistance to signaling. This ambivalent mode of action makes the effect of FTY720 in vivo rather unpredictable. Functionally improved receptor binding molecules including antagonistic antibodies are in AMN107 preparation, but the low availability of properly folded purified G protein-coupled receptors required for the specific selection of binders has limited premature enthusiasm in the field. Both the antibody and the StSPL approaches target S1P function on the level of cell surface receptor activation. S1P is produced by sphingosine kinases and acts as an intracellular modulator of the sphingosine rheostat to promote cell survival, proliferation and various other biological effects. Intracellular S1P lyase usually keeps the pool of free S1P in check, thereby controlling its pro survival function against the pro-apoptotic effects of sphingosine and ceramide in the rheostat. Accordingly, knockdown of intracellular S1P lyase in cancer cells was shown to disrupt apoptosis and results in chemoresistance by Bcl-2/Bcl-xL upregulation. Elevated S1P is causative or at least contributory to various pathophysiologic disorders.