In vivo efficacy of neocarzinostatin coupled with Fab human/mouse chimeric monoclonal antibody A7 against human colorectal cancer.
The anticancer polypeptide neocarzinostatin (NCS) was covalently coupled to a human/mouse chimeric Fab A7 monoclonal antibody (chFabA7) and the in vivo efficacy of this conjugate was examined. NCS concentration assay was carried out, and acute toxicity and tumoricidal effects were examined. The concentration assay, using anti-NCS monoclonal antibody, revealed that administration of the chA7Fab conjugate leads to a greater blood retention and a higher tumor accumulation of NCS, when compared to free NCS administration. The tumoricidal effect of chA7Fab-NCS was higher than that of either free NCS or the saline control, against antigen-positive tumors. In antigen-negative tumors there was no difference in toxic effect among the three preparations. Values of LD50, reflecting acute toxicity, were 5050 U/kg and 3600 U/kg for the chA7Fab-NCS and the free NCS, respectively. These results suggest that chFabA7-NCS may be a promising tool for targeting cancer chemotherapy.
Yamaguchi
T
T
First Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto.
Tsurumi
H
H
Kotani
T
T
Yamaoka
N
N
Otsuji
E
E
Kitamura
K
K
Takahashi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use* / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D009353:Zinostatin / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins; D009353:Zinostatin