MONOCLONAL-ANTIBODY C242-PSEUDOMONAS EXOTOXIN-A - A SPECIFIC AND POTENT IMMUNOTOXIN WITH ANTITUMOR-ACTIVITY ON A HUMAN COLON CANCER XENOGRAFT IN NUDE-MICE

被引:36
作者
DEBINSKI, W [1 ]
KARLSSON, B [1 ]
LINDHOLM, L [1 ]
SIEGALL, CB [1 ]
WILLINGHAM, MC [1 ]
FITZGERALD, D [1 ]
PASTAN, I [1 ]
机构
[1] PHARM CANAG, S-40242 GOTHENBURG, SWEDEN
关键词
COLON CANCER; IMMUNOTOXINS; PSEUDOMONAS EXOTOXIN-A; SOLID TUMOR THERAPY;
D O I
10.1172/JCI115875
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Two immunotoxins were constructed by chemically coupling the monoclonal antibody C242 to Pseudomonas exotoxin A (PE) or a modified form, NlysPE40, that lacks the cell binding domain of PE. Monoclonal antibody C242 recognizes a specific sialylated carbohydrate epitope on a high molecular weight membrane glycoprotein present on cells of human colon, pancreatic, and cervical cancers. C242-PE and C242-NlysPE40 were very cytotoxic for cells expressing this antigen with 50% inhibition of protein synthesis occurring on Colo205 cells at 0.2 ng/ml (0.9 pM) for C242-PE and 6.0 ng/ml (31 pM) for C242-NlysPE40. The two immunotoxins also exhibited a strong antitumor effect on a human colon cancer xenograft grown in nude mice. The specificity and potency of these two C242 immunotoxins warrant their further development for the treatment of cancer.
引用
收藏
页码:405 / 411
页数:7
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