Radioimmunotherapy of Nude Mice Bearing Human Colon Carcinoma with I-131 Labeled Anti-carcinoembryonic Antigen Monoclonal Antibody

누드마우스에 이식된 인체대장암에서 I-131표지 항태아성암항원 단일클론항체를 이용한 방사면역치료법 : 치료성적에 관계되는 인자분석

This study was designed to evaluate the effects of various factors on the therapeutic effect of the I-131 labeled anti-carcinoembryonic antigen monoclonal antibody(anti-CEA antibody). Tetrazolium-based colorimetric assay (MTT) was used to compare in vitro cytotoxicity of 3 Korean colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5) for selection of proper 2 cell lines in this study. The changes of the size of tumor which was xenografted to nude mice (balb/c nu/nu) were compared in 4 groups (group treated I-131 labeled anti-CEA antibody, group treated with non-radiolabeled anti-CEA antibody, group treated with I-131 labeled anti-human chorionic gonadotropin monoclonal antibody (anti-hCG antibody) as nonspecific antibody, and group injected with normal saline as a control). Immunohistochemical staining and in vivo autoradiography were performed after excision of the xenografted tumor. The results were as below mentioned. The in vitro cytotoxic effect of I-131 labeled anti-CEA antibody is most prominent in SNU-C5 cell line between 3 cancer cell lines. The changes of xenografted tumor size in both SNU-C4 and SNU-5S cell tumors at the thirteenth day after injection of the antibodies were smallest in the group treated with I-131 labeled anti-CEA antibody (SNU-C4/SNU-C5; 324/342%) comparing with other groups, group treated with anti-CEA antibody (622/660%), group treated with I-131 anti-hCG antibody (538/546%), and control group(1030/724%)(P<0.02 in SNU-C4 and P<0.1 in SNU-C5 at the 13th day after injection of antibodies). On the thirteenth day after injection of the antibodies nude mice were sacreficed to count the radiouptake of tumor and to check the changes of tumor size. Correlations between radiouptake and change of tumor size were calculated in each groups and significant negative correlation was only obtained in the group treated with I-131 anti-CEA antibody (p<0.05). There were no correlations between antigenic expression of carcinoembryonic antigen and distribution of anti-CEA antibody in both SNU-C4 and SNU-C5 cell tumors on immunoperoxidase staining. On in vivo autoradiography the distributions of anti-CEA antibody were heterogeneous and the intensities of binding were various in SNU-C4 and SNU-C5 cell tumors. It is concluded that I-131 labeled tumor-specific monoclonal antibody, anti-CEA antibody is effective in suppressing the xenografted tumor growth and the effect is influenced by sensitivity of tumor cell itself to the radiolabeled antibody and other local factors instead of specificity of antibody.