[Experimental studies on immunotargeting therapy for esophageal carcinoma].
We produced two types of murine monoclonal antibodies, KYSM-1 and KIS-1, against human squamous cell carcinoma of the esophagus for quantitative diagnosis and optimum therapy. The isotypes of KYSM-1 and KIS-1 were IgM and IgG1, respectively. Immunohistochemical staining demonstrated that both antibodies strongly reacted with human carcinoma cell lines of the esophagus, lung and oral cavity. Fluorescence activated cell sorter analysis demonstrated that each antigen of KYSM-1 and KIS-1 exposed to cellular membrane of squamous carcinoma cells and molecular weights of these antigens detected by KYSM-1 and KIS-1 were 60 kDa and 90 kDa, respectively, in non-reduced condition. These 2 monoclonal antibodies were labeled with 125I by the Iodogen method, and each antibody was injected into nude mice with human squamous cell carcinoma of the esophagus. Regarding in vivo accumulation of 125I-labeled antibodies, however, KIS-1 alone showed significantly high values in the tumor at 5 and 7 days after the injection. From this result, KIS-1 was labeled with 131I and injected into the tumor-bearing mice with a dose of 200 microCi. Moderately effective results were found in the tumor by 14 days after the injection. Furthermore, KIS-1 was also conjugated to peplomycin (PEP). In in vitro and in vivo effects of targeting chemotherapy, the conjugates killed human squamous carcinoma cells and tumor-implanted nude mice. These results suggest that the 131I-labeled KIS-1 and/or KIS-1-PEP conjugate may provide a targeting therapy in patients with squamous cell carcinoma of the esophagus.
Yamana
H
H
First Dept. of Surgery, Kurume University School of Medicine.
Kakegawa
T
T
Tanaka
T
T
Higaki
K
K
Fujii
T
T
Tou
U
U
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D004938:Esophageal Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017663:Peplomycin / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D017663:Peplomycin