ANTIBODY-TARGETED PHOTOLYSIS - SELECTIVE PHOTODESTRUCTION OF HUMAN T-CELL LEUKEMIA-CELLS USING MONOCLONAL ANTIBODY-CHLORIN E6 CONJUGATES
ANTIBODY-TARGETED PHOTOLYSIS - SELECTIVE PHOTODESTRUCTION OF HUMAN T-CELL LEUKEMIA-CELLS USING MONOCLONAL ANTIBODY-CHLORIN E6 CONJUGATES
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DOI：
10.1073/pnas.83.22.8744
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发表时间：
1986-11-01
影响因子：
11.1
通讯作者：
YARMUSH, ML
中科院分区：
文献类型：
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作者：
OSEROFF, AR;OHUOHA, D;YARMUSH, ML
使用光敏剂二氢卟酚e6通过葡聚糖分子偶联到抗T细胞单克隆抗体（mAb）抗Leu-1，完成HPB-ALL人T细胞白血病细胞的选择性体外光破坏。mAb/二氢卟酚摩尔比高达1：36的偶联物保留了mAb结合活性，并且结合二氢卟酚的单线态氧产生的吸收光谱和量子效率（0.7 ± 0.01）。0.2)与游离光敏剂相比无变化。光毒性，通过克隆形成试验和溴化乙锭的吸收来测量，依赖于mAb-二氢卟酚和630- 670-nm光的剂量，通过2 H2O增强，并且仅在结合mAb的目标群体中观察到。类似地，溶液中的游离二氢卟酚e6在比mAb携带的量多100倍的量下没有光动力学效应。对于这种抗体靶向系统，杀死一个细胞需要大约1010个单线态氧分子。
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 1010 molecules of singlet oxygen were necessary to kill a cell.