CD137: Recent Pub from SBIR collaborators (L. Chen and S. Strome) using transgenic goat derived CD137 mab. They include a nice comparison non-glycosylated to low fucose content versions of the the mab. For some strange reason this mab works to ameliorate auto-immune diseases even though the mechanism of action is supposed to cause CD8 activity enhancement. I am not an expert that is just my first read take on their words. The bottom line seems to be that not only would this enhance immune response to late stage cancers but also could be useful for auto-immune disorders like RA and lupus.
1: Blood. 2008 Jun 2. [Epub ahead of print]
Fc dependent expression of CD137 on human NK cells: insights into "agonistic" effects of anti-CD137 monoclonal antibodies.
Lin W, Voskens CJ, Zhang X, Schindler DG, Wood A, Burch E, Wei Y, Chen L, Tian G, Tamada K, Wang LX, Schulze DH, Mann D, Strome SE.
Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland,
Baltimore, MD, United States.
CD137 (4-1BB) is a co-stimulatory molecule which can be manipulated for the treatment of cancer and autoimmune disease. While agonistic antibodies (mAb's) against CD137 enhance the rejection of murine tumors in a natural killer (NK) and T cell dependent fashion, the mechanism for NK dependence is poorly understood. In this study, we evaluated the ability of two different glycoforms of a chimerized anti-human CD137 mAb, an aglycosylated (GA) and a low fucose form (GG), to react with human NK cells. Both mAb's bound similarly to CD137, were competitively inhibited by the parental mAb and partially blocked the interaction between CD137 and CD137Ligand. However, unlike GA mAb, immobilized GG mAb activated NK cells and enhanced CD137 expression. These effects were seemingly dependent on Fc interaction with putative Fc-receptors on the NK cell surface, as
only the immobilized Fc-fragment of GG was required for CD137 expression. Furthermore, CD137 expression could be enhanced with antibodies directed against non-CD137 epitopes, and the expression levels directly correlated with patterns of Fc-glycosylation recognized to improve Fc interaction with Fcgamma-receptors. Our data suggest that CD137 can be enhanced on NK cells in an Fc dependent fashion and that expression correlates with phenotypic and functional parameters
of activation.
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