Fundamental Studies on New Effective Diagnosis and Treatment for Esophageal Carcinomas by using Monoclonal Antibody and its Fragment.

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We had produced two types of monoclonal antibodies, KYSM-1 and KIS-1, against human squamous cell carcinoma of the esophagus for quantitaive diagnosis and optimum therapy. The isotype of KYSM-1 and KIS-1 were IgM and IgG1, respectively. These two antibodies were treated by papain to get their fragment. KYSM-1 fragment F[ab']2u and KIS-1 fragment F[ab']2 and Fab were obtained.Reactivities of these fragments were analyzed by ELISR.Reactivities of all fragments were reduced after the treatment, -28% in KYSM-1 f[ab']2u, -22% in KIS-1 F[ab']2 and -60% in KIS-1 Fab. These monoclonal antibodies and their fragments were lebeled with ^<125>I or ^<131>I by the lodogen method, and each antibody was injected into nude mice with human squamous cell carcinoma of the esophagus [KE-1]. Regarding in vivo accumulation of ^<125>I - or ^<131>I - labeled antibodies, however, ^<125>I - labeled KIS-1 F[ab']2 alone showed significantly high values in the tumor at 3 days after the injection. While, ^<125>I - labeled intact KIS-1 also showed significantly high values in the tumor by 7 days. From these results, Intact KIS-1 and KIS-1 F[ab'] 2 were labeled with ^<131>I and each or both of them were injected into the tumor-bearing nude mice with a total dose of 250uCI.The most significant inhibition of the tumor growth was noted in the mixed administration of intact and fragment KIS-1.These results suggest that the mixed administration of ^<131>I - labeled intact KIS-1 and KIS-1 F[ab']2 may provide a quantitative tumor imaging and a targeting therapy in patients with esophageal carcinoma.