Clayton Reginald, Ohagen Asa, Goethals Olivia, Smets Alexandra, Van Loock Marnix, Michiels Lieve, Kennedy-Johnston Erin, Cunningham Mark, Jiang Haiyan, Bola Sharon, Gutshall Lester, Gunn George, Del Vecchio Alfred, Sarisky Robert, Hallenberger Sabine, Hertogs Kurt
Tibotec BVBA, Generaal De Wittelaan L 11B 3, 2800 Mechelen, Belgium.
J Virol Methods. 2007 Jan;139(1):17-23. doi: 10.1016/j.jviromet.2006.08.017. Epub 2006 Oct 10.
The use of targeting moieties is a new and exciting field of scientific research for facilitating the specific delivery of therapeutic agents in HIV-infected patients. The interaction of a potential targeting moiety with its ligand is a crucial factor in the evaluation of a targeted approach for chemotherapeutic intervention. Therefore, we have further characterized the interaction between a potential targeting agent, the monoclonal human antibody F105, and its ligand gp120, a glycoprotein expressed on the surface of HIV-1 infected cells. We demonstrate the specificity of binding and entry of F105 to infected cells. F105 was rapidly taken up into the cell and accumulated in the Golgi apparatus. Kinetic analysis of the F105-gp120 interaction revealed an equilibrium dissociation constant (K(D)) of 0.62 nM, compared with the gp120-CD4 interaction where the K(D) was determined at 35 nM. Consequently, F105 displayed a higher gp120 affinity. This was due to a slower dissociation as compared with the natural ligand. These data further underline the potential of monoclonal antibodies as targeting agents, and offer new insights into the possibility of F105 as a targeting moiety for the delivery of antiretroviral drugs to HIV-1 infected cells.
使用靶向部分是科学研究中一个全新且令人兴奋的领域，有助于在HIV感染患者中实现治疗药物的特异性递送。潜在靶向部分与其配体之间的相互作用是评估化疗干预靶向方法的关键因素。因此，我们进一步表征了一种潜在靶向剂——人源单克隆抗体F105与其配体gp120（一种在HIV-1感染细胞表面表达的糖蛋白）之间的相互作用。我们证明了F105与感染细胞结合和进入的特异性。F105迅速被细胞摄取并积聚在高尔基体中。F105与gp120相互作用的动力学分析显示平衡解离常数（K(D)）为0.62 nM，而gp120与CD4相互作用的K(D)为35 nM。因此，F105表现出更高的gp120亲和力。这是由于与天然配体相比解离较慢。这些数据进一步强调了单克隆抗体作为靶向剂的潜力，并为F105作为将抗逆转录病毒药物递送至HIV-1感染细胞的靶向部分的可能性提供了新的见解。
