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抗体靶向光解:使用单克隆抗体-二氢卟吩e6偶联物对人T细胞白血病细胞进行选择性光破坏

Antibody-targeted photolysis: selective photodestruction of human T-cell leukemia cells using monoclonal antibody-chlorin e6 conjugates.

作者信息

Oseroff A R, Ohuoha D, Hasan T, Bommer J C, Yarmush M L

出版信息

Proc Natl Acad Sci U S A. 1986 Nov;83(22):8744-8. doi: 10.1073/pnas.83.22.8744.

Abstract

Selective in vitro photodestruction of HPB-ALL human T-cell leukemia cells was accomplished using the photosensitizer chlorin e6 coupled through dextran molecules to an anti-T-cell monoclonal antibody (mAb), anti-Leu-1. Conjugates with mAb/chlorin molar ratios as high as 1:36 retained mAb binding activity, and the absorption spectrum and quantum efficiency for singlet oxygen production of bound chlorin (0.7 +/- 0.2) were unchanged from that of the free photosensitizer. Phototoxicity, as measured by a clonogenic assay and by uptake of ethidium bromide, was dependent on the doses of both mAb-chlorin and 630- to 670-nm light, was enhanced by 2H2O, and was observed only in target populations that bound the mAb. Similarly, free chlorin e6 in solution had no photodynamic effect in amounts 100 times more than that carried by the mAb. For this antibody-targeted system, approximately 10(10) molecules of singlet oxygen were necessary to kill a cell.

摘要

通过将光敏剂二氢卟吩e6通过葡聚糖分子与抗T细胞单克隆抗体(mAb)抗-Leu-1偶联,实现了对HPB-ALL人T细胞白血病细胞的体外选择性光破坏。单克隆抗体/二氢卟吩摩尔比高达1:36的偶联物保留了单克隆抗体的结合活性,并且结合的二氢卟吩产生单线态氧的吸收光谱和量子效率(0.7±0.2)与游离光敏剂的相同。通过克隆形成试验和溴化乙锭摄取测量的光毒性取决于单克隆抗体-二氢卟吩和630至670nm光的剂量,被2H2O增强,并且仅在结合单克隆抗体的靶细胞群体中观察到。同样,溶液中的游离二氢卟吩e6在比单克隆抗体携带量多100倍的量时没有光动力效应。对于这个抗体靶向系统,杀死一个细胞大约需要10(10)个单线态氧分子。

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