Applicability of monoclonal antibody Fab fragments as a carrier of neocarzinostatin in targeting chemotherapy.
Two types of fragments of MAb A7 were produced to improve the efficacy and safety in targeting chemotherapy with neocarzinostatin. In this study, 125I-labeled F(ab')2 and Fab fragments of MAb A7 and 125I-labeled MAb A7 were injected intravenously into mice with pancreatic carcinoma xenografts, and the accumulation of each antibody in the tumors was compared. A greater amount of the 125I-labeled Fab fragments of MAb A7 localized in the tumor 2 h following the injection than was observed with the other probes. Relatively less 125I-labeled MAb A7 localized in the tumor 2 h following the injection than was observed with the other two probes. Moreover, reaction of rabbit antimouse IgC with the Fc portion, which is the most immunopotent region of the Fab and F(ab')2 fragments of MAb A7 and MAb A7, was determined by ELISA; the weakest reaction was observed with the Fab fragments of MAb A7. These results suggest that the Fab fragments of MAb A7 may be more suitable carriers of an anticancer drug that is inactivated rapidly in the blood, such as NCS, in targeting chemotherapy than either intact MAb A7 or the F(ab')2 fragments of MAb A7.
Otsuji
E
E
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Yamaguchi
T
T
Tsuruta
H
H
Yata
Y
Y
Nishi
H
H
Okamoto
K
K
Taniguchi
K
K
Kato
M
M
Kotani
T
T
Kitamura
K
K
Takahashi
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D014407:Tumor Cells, Cultured; D009353:Zinostatin / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D009353:Zinostatin