THERAPEUTIC ANTICD23 ANTIBODY DIMERS FOR CLL

我们的长期目标是开发四价免疫球蛋白/免疫球蛋白单抗二聚体，用于治疗过度表达CD23膜抗原的白血病和淋巴瘤患者。使用CD20和CD23 B细胞膜抗原的初步数据清楚地表明，超交联会诱导细胞凋亡和生长抑制。相比之下，单抗与膜抗原的直接结合效率较低。开发的方法允许使用在重链上的特定位置引入半胱氨酸反应性硫醇的基因工程抗体来制备具有生物活性的mAb二聚体，该二聚体保留完整的效应器功能。通过仔细选择引入硫醇的位置，二聚体应该比单体单抗具有更好的产率和更好的生物学特性。拟议的商业应用：该项目的目标是开发一种四价抗CD23抗体二聚体，使其能够更有效地治疗慢性淋巴细胞白血病。

Our long term objective is to develop tetravalent IgG/IgG monoclonal antibody dimers for treating leukemia and lymphoma patients over-expressing the CD23 membrane antigens. Preliminary data using both CD20 and CD23 B-cell membrane antigens has clearly demonstrated that hyper-cross linking induces both apoptosis and growth inhibition. In contrast, direct binding of monomeric monoclonal antibody (mAb) to membrane antigen was inefficient. The process developed allows for the preparation of biologically active mAb dimers that retain full effector functions, using a genetically engineered antibody having the cysteine reactive thiol introduced at a specific site on the heavy chain. By careful selection of the site for thiol introduction, dimers should be produced having excellent yields and a superior biological profile than monomeric mAb. PROPOSED COMMERCIAL APPLICATION: The goal of this project is to develop a tetravalent anti-CD23 antibody dimer that will allow for more potent and effective treatment for chronic lymphocytic leukemia.