The latter two values were not statistically different from those found in healthy control animals . The effect of mAb 8B6 treatment was not statistically different from that obtained upon treatment with mAb 14G2a . The specificity of mAb 8B6 therapy was again demonstrated, since treatment with an equivalent amount of nonspecific antibody was completely ineffective. Taken together, our results show the potential therapeutic efficacy of mAb 8B6 for the treatment of GD2/OAcGD2-expressing tumors. The most striking result of this study is that mAb 8B6, a mouse monoclonal antibody specific for PF-2341066 biological activity OAcGD2 that does not bind GD2, did not show any reactivity at all with peripheral nerves. By contrast, the anti-GD2 antibody 14G2a that was used as a positive control stained peripheral nerve fibers, which are known to express GD2 . In these study, we selected an immunoperoxydase assay performed on frozen tissue sections according to the FDA guidelines . In the absence of characterization of the Oacetyl- transferase, the enzyme responsible for the biosynthesis of O-acetylated ganglioside , the results suggest that GD2 is differentially acetylated in normal and tumor tissue and that normal tissues expressing GD2 may not express OAcGD2, as is known for GD3 . Antibody 8B6 did not stain or stain very weakly the normal tissues that must be tested before clinical tested, as required by the FDA, with the exception of lymph node germinal centers. This exception may be considered as a positive control for the ICH study since GD2 has been shown to be expressed in lymph node germinal centers . As mentioned earlier, the therapeutic use of anti-GD2 mAbs is associated with important neurotoxic effects in patients. The proposed cause of this dose-limiting toxicity is the binding of anti- GD2 antibodies to GD2 expressed on normal nerve cells followed by complement deposition on the nerve cell surface . Hence, our data suggest that mAbs specific for OAcGD2 should be less toxic because they do not bind to peripheral nerves, thereby allowing dose escalation of antibodies. Some other side effects observed in patients after anti-GD2 mAb infusions included hematopoietic suppression and a syndrome of inappropriate antidiuretic hormone .
This enzyme catalyses the reverse reaction thus playing a protective role against enhanced
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