THERAPEUTIC ANTICD23 ANTIBODY DIMERS FOR CLL

我们的长期目标是开发四价IgG/IgG单克隆抗体二聚体，用于治疗过表达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，超交联可诱导细胞凋亡和生长抑制。相比之下，单克隆抗体（mAb）直接与膜抗原结合的效率较低。所开发的工艺允许制备具有生物活性的mAb二聚体，保留完整的效应功能，使用在重链上的特定位点引入半胱氨酸活性硫醇的基因工程抗体。通过对巯基引入位点的仔细选择，二聚体应该比单抗具有优异的产量和优越的生物学特征。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，这将使慢性淋巴细胞白血病的治疗更加有效。

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.