[Inhibition of the growth of hepatoma and hepatic metastasis by pingyangmycin conjugated with Fab' fragment of monoclonal antibody].
OBJECTIVE
To develop an immunoconjugate with inhibitory effect on the growth of hepatoma and hepatic metastasis of tumor by linking Fab' fragment of monoclona antibody (McAb) to pingyangmycin (PYM).


METHODS
Monoclonal antibody Fab' fragment was obtained by enzymolysis with pepsin and DTT reduction. Linking of the Fab' fragment and PYM was mediated by dextran T40. Indirect ELISA, TTC bacteriostatic titer test, clonogenic assay and animal models transplanted with tumor were used to assess the biological activities and antitumor effects of Fab' PYM conjugate within and without the bodies of 10 mice.


RESULTS
The Fab' PYM conjugate showed immunoreactivity to BEL7402, hepatoma 22 (H22) and HT29 cells, but no reaction to KB cells. The bacteriostatic activity of PYM in the conjugate was 15% as much as that of free PYM. The 50% inhibitory doses (IC50) of Fab'PYM conjugate to BEL7402, HT29 cells and KB cells were 0.02 micromol/L, 0.08 micromol/L and 0.50 micromol/L respectively. Given intravenously, 10 mg/kg x 6, Fab' PYM conjugate and PYM suppressed the growth of hepatoma 22 by 86% and 62% respectively. Given intraperitoneally, 10 mg/kg x 4, Fab' PYM and PYM decreased the hepatic metastasis of colon carcinoma 26 by 91% and 62% respectively.


CONCLUSIONS
Fab' PYM conjugate is more effective in combating hepatoma and hepatic metastasis of tumor than free PYM.
Liu
X
X
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Shang
B
B
Liu
X
X
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control*; D018796:Immunoconjugates / Q000627:therapeutic use*; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D001761:Bleomycin; C021771:zhengguangmycin