The effect of radioimmunotherapy using murine monoclonal antibody KIS1 on esophageal squamous cell carcinoma-bearing nude mice.
The monoclonal antibody (MoAb) KIS1 has been shown to react specifically with an antigen of human squamous cell carcinoma (SCC); however, a major problem in its clinical application is that the intact murine antibody induces a human anti-mouse antibody (HAMA). To overcome this problem, we produced the KIS1 F(ab')2 fragment, then radioiodinated the intact KIS1 antibody and its F(ab')2 fragment. Nude mice bearing human esophageal SCC implants were injected with 100 microCi of 131I-intact KIS1 or 131I-KIS1 F(ab')2, and images were obtained using a gamma camera. Radioimmunotherapy (RIT) was performed by injecting the tumor-bearing nude mice with 131I-intact KIS1 or 131I-KIS1 F(ab')2 at a dosage of 300 microCi, following which 7 or 3 days were required to produce high quality tumor images by scintigraphy. The tumor-bearing mice treated with 131I-KIS1 F(ab')2 showed significant tumor growth inhibition, about 5.4 times greater than that of the control group and 1.8 times greater than that of the 131I-intact KIS1 group 21 days after the injection. These results indicate that the KIS1 F(ab')2 fragment is superior to intact KIS1, and that it may be clinically useful for radioimmunodetection followed by tumor targeting therapy for patients with SCC of the esophagus.
Fujii
T
T
First Department of Surgery, Kurume University School of Medicine, Japan.
Yamana
H
H
Toh
Y
Y
Toh
U
U
Fujita
H
H
Shirouzu
K
K
Morimatsu
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D004938:Esophageal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes