Several anti-GD2 Bortezomib manufacturer antibodies have been developed for clinical use over the past 2 decades, two of which are under evaluation in the clinical setting: ch14.18 and 3F8 . 3F8 is a completely murine antibody and ch14.18 is a human�Cmouse chimeric construct consisting of variable regions derived from the murine anti-GD2 antibody 14G2a and of constant regions of heavy and light chains from a human IgG1 molecule. A recent phase III trial has shown that a combination of anti-GD2 ch14.18 antibody and cytokines with the standard therapy significantly improved outcome . Although these results are very encouraging, one of the major drawbacks of anti-GD2 mAbs is their toxicity. The infusion is frequently associated with severe pain, changes in cardiovascular tone, fever and complement depletion . Furthermore subsequent to treatment with anti-GD2 monoclonal antibody some patients have developed sensorimotor polyneuropathy . These neurotoxic toxicities are most likely the result of mAb recognition of GD2 on pituitary gland and peripheral nerves and complement activation . Hence, they limit the dose of anti- GD2 mAbs that can be given and therefore its clinical efficacy. In an effort to increase the therapeutic index of ch14.18, a humanized antibody was recently designed in which the Fc region was mutated in the CH2 domain to no longer engage C1q. The resultant antibody, hu14.18 K322A, retained potent ADCC activity against GD2-expressing tumor with impaired complement activation in vitro, and, reduced neurotoxic side effects in rat . However, since it still retains its binding activity to peripheral nerve fibers, this format would not be suitable for developing immunotherapeutic agents by conjugation to toxins, radionuclides or other effector molecules. In our laboratory, several anti-disialo-gangliosides antibodies have been generated that recognize GD2, GD3 and acetylated GD2 and GD3. One of these antibodies, mAb 8B6, was shown to be specific for the O-acetylated derivative of GD2 with no cross-reaction with GD2 by thin layer chromatography immunostaining. OAcGD2 is concomitantly expressed by GD2-positive tumor cells . This antibody, mAb 8B6, was not found to cross react with GD3, acetylated GD3 or other gangliosides .