Monoclonal antibody A7 tumor localization enhancement by its F(ab')2 fragments to colon carcinoma xenografts in nude mice.
The monoclonal antibody A7 (MoAb A7), which belongs to IgG1, was digested with pepsin to yield F(ab')2 fragments. The maximum binding to the human colon cancer cell line, SW1116, was 27% with 125-I labeled whole MoAb A7 and 24% with 125-I labeled F(ab')2 fragments using an in vitro binding assay. The results showed that the binding activity of F(ab')2 to SW1116 was practically the same as that of whole MoAb A7. The preferred localization of the fragments to tumor tissue, compared with normal mouse tissue, was demonstrated in mice carrying SW1116 xenografts. The tumor:blood ratio three days after injection was 2.64:18.5 for whole MoAb A7:F(ab')2, respectively. The tissue:blood ratios for the F(ab')2 fragments showed a value of 18.5 in tumors, whereas its was a value less than 1.0 in normal organs. The tumor accumulation of F(ab')2 fragments was also dependent on the antigenic expression of each tumor among xenografts of colon carcinoma SW1116 and WiDr, and squamous cell carcinoma KB. In kinetic experiments with whole MoAb A7 and its F(ab')2 fragments, whole MoAb A7 was lost, with a half-life of 4 days, in both blood and tumors, whereas F(ab')2 fragments were rapidly lost with a half-life of 1.5 days. These results suggested that the F(ab')2 fragments were cleared from the blood faster than was whole MoAb A7.
Kitamura
K
K
Department of Surgery, Kyoto Prefectural University of Medicine.
Takahashi
T
T
Yamaguchi
T
T
Kitai
S
S
Amagai
T
T
Imanishi
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism; D003110:Colonic Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000493:pharmacokinetics*; D007074:Immunoglobulin G / Q000493:pharmacokinetics*; D051379:Mice; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G