Potent and selective 17b-HSD2 inhibitors for the treatment of osteoporosis were recently reported

The immune recognition of GD2 on mesenchymal stromal cells in the marrow microenvironment was suggested to underlie the hematopoietic suppression and anti-GD2 mAb cross-reactivity with the posterior lobe of the pituitary gland is believed to modulate the secretion of antidiuretic hormone resulting in the induction of the XAV-939 syndrome of inappropriate antidiuretic hormone secretion . Interestingly, mAb 8B6 did not show any binding to mesenchymal stromal cells in the bone narrow nor to the posterior lobe of the pituitary gland. We also examined the immunohistochemical OAcGD2 localization in a number of malignant tissues and found that mAb 8B6 showed strong reactivity with neuroectodermic tumor biopsy tissues, such as melanoma and neuroblastoma similar to previous investigations . We further demonstrated the high expression of OAcGD2 at the tumor cell surface by Scatchard analysis in vitro. In the 7 tested cell lines, the average of sites/cell ranged from 50,000 sites/cell up to 56106 sites/cell. The expression level of OAcGD2 in cell lines was first described based on extraction and thin layer chromatography or immune TLC . These methods cannot discriminate the membrane from intracellular OAcGD2 cell content. Importantly, our data shows that the amount of OAcGD2 molecules present at the cell surface is comparable, though lower, to that of mAb 14G2a epitope. However, the number of GD2 molecules calculated here may be overestimated as previous reports suggested that mAb 14G2a cross-reacts with OAcGD2 . In agreement with this earlier study, we did see a slight crossreactivity of mAb 14G2a against OAcGD2 in immuno-TLC experiments . Scatchard analysis further showed that mAb 8B6 and mAb 14G2a displayed equivalent binding affinities for their respective epitopes that were within the range anti-GD2 antibodies . OAcGD2 expression was confirmed on all of the 12 neuroblastoma tumor sections tested. This is consistent with a previous study reported by Ye and Cheung that OAcGD2 is a naturally occurring GD2 derivative in neuroblastoma tumors. We also showed that OAcGD2 is a pro-apoptotic constituent activated on binding with hostile antibodies.

Leave a Reply

Your email address will not be published.