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Trichosanthin-monoclonal Antibody Conjugate Specifically Cytotoxic to Human Hepatoma Cells in Vitro¹

Shanghai Institute of Biochemistry [Q-c. W., Z-c. Z.], Shanghai Institute of Cell Biology [H. X., Z. H. Y.], and Academia Sinica, Shanghai 200031, Department of Pharmacology, Shanghai College of Traditional Chinese Medicine [W-b. Y., L-q. L.], Shanghai 200032

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.

¹ Supported by Grants of the Bio-High Technology Program from the Chinese Committee of Science and Technology and Grants for Key Research Projects in the 7th Five-year Plan from the Ministry of Health of China.

² To whom requests for reprints should be addressed, at Shanghai Institute of Biochemistry, Academia Sinica, 320 Yue-yang Road, Shanghai 200031, China.

Received 8/14/89. Accepted 4/16/91.