Pincus S H, Wehrly K, Chesebro B
Laboratory of Microbial Structure and Function, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840.
J Immunol. 1989 May 1;142(9):3070-5.
mAb 907 is directed against the envelope protein of the HIV. The epitope recognized by this antibody is expressed in moderate density on the surface of tissue culture cells infected with the LAV/HTLV-IIIB strain of HIV. We have coupled antibody 907 to ricin A chain (RAC). The antibody-RAC conjugate inhibited protein synthesis and cell growth in HIV-infected cells. An irrelevant antibody conjugated to RAC had no effect. Most important, treatment of infected cells with the conjugate markedly inhibited the production of infectious virus, as measured by the production of viral foci on susceptible monolayer cells. Exposure of HIV-infected target cells to the conjugate for as short a period as 1 h resulted in cell death. Serum of AIDS patients inhibited, but did not completely suppress, the toxicity of the 907-RAC conjugate. A second antibody, designated BM-1, which recognizes a carbohydrate Ag on the surface of virally infected cells, was conjugated to RAC. The BM-1-RAC conjugate did not kill HIV-infected cells, highlighting the importance of the target Ag. Immunotoxins produced with antibodies that recognize Ag on the surface of HIV-infected cells may have utility in the therapy of AIDS.
单克隆抗体907针对的是HIV的包膜蛋白。该抗体识别的表位在感染了HIV的LAV/HTLV-IIIB毒株的组织培养细胞表面以中等密度表达。我们已将抗体907与蓖麻毒素A链（RAC）偶联。抗体-RAC偶联物抑制了HIV感染细胞中的蛋白质合成和细胞生长。与RAC偶联的无关抗体则没有作用。最重要的是，用该偶联物处理感染细胞可显著抑制感染性病毒的产生，这通过在易感单层细胞上产生病毒灶来衡量。将HIV感染的靶细胞暴露于该偶联物仅1小时就导致细胞死亡。艾滋病患者的血清可抑制但不能完全抑制907-RAC偶联物的毒性。另一种名为BM-1的抗体识别病毒感染细胞表面的一种碳水化合物抗原，将其与RAC偶联。BM-1-RAC偶联物不会杀死HIV感染的细胞，这突出了靶抗原的重要性。用识别HIV感染细胞表面抗原的抗体产生的免疫毒素可能在艾滋病治疗中具有应用价值。
