The role of monoclonal antibody A7 as a drug modifier in cancer therapy.
An anticancer antibiotic, neocarzinostatin (NCS), was covalently conjugated to the murine monoclonal antibody A7 (mAb A7), which recognizes the glycoprotein on the cell surface of human colon cancer. The biological and pharmacological properties of the conjugate (A7-NCS) were examined and compared with those of unconjugated NCS. A7-NCS exhibited a strong binding and cytotoxicity to the cell and an antigen-specific tumor accumulation. Significant tumoricidal effects in vivo were observed in the antigen-positive tumor-bearing mice treated with A7-NCS, whereas NCS mixed with mAb A7 and NCS alone were relatively ineffective. In the antigen-negative tumor, the tumoricidal effect of A7-NCS was lower than in the antigen-positive tumor. The NCS concentration in blood and tumor were significantly elevated by conjugation to mAb A7. The NCS localization in tumor was higher in the antigen-positive tumor than in the antigen-negative tumor. Death due to acute toxicity was observed at a dose of 20 units (U) NCS in mice treated with unconjugated NCS, whereas toxicity was seen with a much higher dose of NCS (100 U) if the drug was conjugated to the mAb. These findings show that mAb A7 confers more favorable pharmacological properties on an anticancer drug, making it potentially more useful for cancer chemotherapy.
Kitamura
K
K
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Miyagaki
T
T
Yamaoka
N
N
Tsurumi
H
H
Noguchi
A
A
Yamaguchi
T
T
Takahashi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D000922:Immunotoxins / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D009353:Zinostatin / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D009353:Zinostatin