Davis A A, Whidby D E, Privette T, Houston L L, Hunt R C
Department of Microbiology, University of South Carolina School of Medicine, Columbia 29208.
Invest Ophthalmol Vis Sci. 1990 Dec;31(12):2514-9.
An immunotoxin conjugate of a murine monoclonal antibody against human transferrin receptors and the A chain of ricin was examined for its potential to inhibit selectively the growth of retinal pigment epithelial (RPE) cells which grow in an uncontrolled manner in proliferative vitreoretinopathy. The probable efficacy of such an agent in vivo stems from the observation that actively proliferating cells possess many more transferrin receptors than normal quiescent cells. The authors showed in vitro that the immunoconjugate (454A12 MAB-rRA) inhibits protein synthesis in actively dividing RPE cells but has a smaller or no effect on protein synthesis by confluent, nondividing RPE cells. The effect was specific in that neither the free ricin A chain (rRA) nor the monoclonal antibody (454A12 MAB) alone has any inhibitory effect. Furthermore, the antibody competes with the immunotoxin and suppresses the latter's toxicity. This immunotoxin has applications for therapy in conditions in which the pathologic proliferation of RPE cells occurs.
一种针对人转铁蛋白受体的鼠单克隆抗体与蓖麻毒素A链的免疫毒素偶联物，被检测其选择性抑制增殖性玻璃体视网膜病变中以不受控制方式生长的视网膜色素上皮（RPE）细胞生长的潜力。这种药物在体内可能的疗效源于这样的观察结果：活跃增殖的细胞比正常静止细胞拥有更多的转铁蛋白受体。作者在体外表明，免疫偶联物（454A12 MAB-rRA）抑制活跃分裂的RPE细胞中的蛋白质合成，但对汇合的、不分裂的RPE细胞的蛋白质合成影响较小或无影响。这种作用是特异性的，因为单独的游离蓖麻毒素A链（rRA）或单克隆抗体（454A12 MAB）都没有任何抑制作用。此外，该抗体与免疫毒素竞争并抑制后者的毒性。这种免疫毒素可用于治疗RPE细胞发生病理性增殖的病症。
