A monoclonal antibody for esophageal squamous cell carcinoma and immunotargeting therapy.

T. Tanaka MDa,b, U. Toh MDb, T. Fujii MDb, S. Sueyoshi MDb, H. Fujita MDb, K. Shirouzu MDb, H. Yamana MDa.

aMultidisciplinary treatment center and bDepartment of Surgery, Kurume University School of Medicine, Kurume, Japan

Aim : To clarify the antigenicity of our new monoclonal antibody for human esophageal squamous cell carcinoma and develop the targeting therapy using this antibody. Methods : A monoclonal antibody (mAb), KIS-1, was developed by immunization of BALB/c mice with human squamous cell carcinoma cell line, KE-2, established in our department. Reactivity of KIS-1 in panel of cancer cell lines and surgical specimens from patients with squamous cell carcinoma (SCC) of the esophagus, oral cavity, lung and cervix were screened with immunohistochemical staining and immunoblot analysis. KIS-1 labeled with 125 I was injected into nude mice bearing human SCC and in vivo distribution was examined. Furthermore, KIS-1 was conjugated to 131I and vindedine (VDS) , and the anti-tumor effect of these conjugates in tumor (SCC) bearing mice was examined. Results : KIS-1 mainly recognized a membrane antigen expressed on the majority of esophageal, lung, oral and cervix SCC. In contrast, there was little reactivity to gastric, colorectal or lung adenocarcinoma. 131I-KIS-1 conjugate significantly accumulated in SCC tumor by 7th days after the injection and showed significant inhibitory effect on tumor growth. VDS-KIS-1 conjugate had 2-fold greater inhibitory effect on tumor growth compared with VDS alone. Conclusion : KIS-1 is a highly specific monoclonal antibody for human SCC. The KIS-1 may be a new tool for understanding the antigenicity of SCC and for immunotargeting therapy in patients with SCC.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Immunotherapy.