Trichosanthin-monoclonal antibody conjugate specifically cytotoxic to human hepatoma cells in vitro.
A plant single-chain ribosome-inactivating protein derived from the root tuber of Trichosanthes kirilowii, termed trichosanthin (TCS), was modified with 2-iminothiolane. It was not like trichokirin, a ribosome-inactivating protein derived from the seeds of the same plant, in that TCS retained full activity when 1.5 sulfhydryl groups were introduced into each TCS molecule by 2-iminothiolane modification. The 2-iminothiolane-TCS was conjugated to Hepama-1, a monoclonal antibody directed against human hepatoma with a cross-linking reagent, N-succinimidyl-3-(2-pyridyl)-dithiopropionate. The hepatoma cytotoxicity of the immunotoxin, TCS-Hepama-1, was 500-fold higher than that of free TCS and only 1 log lower than that of free ricin. However, the immunotoxin was approximately 600-fold less cytotoxic to HeLa cells. The results suggested that the immunotoxin was a potent and quite specific antihepatoma agent and might have considerable potential in hepatoma therapy.
Wang
Q C
QC
Shanghai Institute of Biochemistry, China.
Ying
W B
WB
Xie
H
H
Zhang
Z C
ZC
Yang
Z H
ZH
Ling
L Q
LQ
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D000922:Immunotoxins / Q000633:toxicity*; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000628:therapy; D014176:Protein Biosynthesis; D015978:Trichosanthin / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D015978:Trichosanthin