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Selective cytotoxicity of adriamycin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma in vitro and in vivo
Authors:Kaneta Y  Tsukazaki K  Kubushiro K  Sakayori M  Ueda M  Nozawa S
Affiliation:Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
Abstract:Missile therapy, which destroys cancer cells specifically, has been regarded as an effective treatment modality for carcinoma. The monoclonal antibody MSN-1 (IgM), which reacts strongly with endometrial adenocarcinomas, was combined with adriamycin (ADM) by a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolane. Its selective cytotoxicity against SNG-II was examined in a colony formation in vitro, and on athymic mice in vivo. The results of our study suggest that the or IC50, of the MSN-1-ADM immunoconjugate against SNG-II to be 57 times that of ADM alone in vitro. The reductions in resected weights of target tumor cells, at the local site of the MSN-1-ADM immunoconjugate treatment, were 25% with caudal vein administration, and 38% with local administration, as compared with the untreated group, in vivo. There was no weight loss in treated mice. Our results suggest that this MSN-1-ADM immunoconjugate has potential clinical application in the treatment of endometrial adenocarcinomas.
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