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Growth suppression of human colorectal carcinoma in nude mice by monoclonal antibody C27‐abrin A chain conjugate

 

作者: Lai‐Chen Tsai,   Yung‐Liang Chen,   Chung Lee,   Horng‐Min Chen,   Zo‐Nan Chang,   Mei‐Whey Hung,   Pei‐Ling Chao,   Jung‐Yaw Lin,  

 

期刊: Diseases of the Colon & Rectum  (OVID Available online 1995)
卷期: Volume 38, issue 10  

页码: 1067-1074

 

ISSN:0012-3706

 

年代: 1995

 

出版商: OVID

 

关键词: Colorectal carcinoma;Abrin A chain immunoconjugate;Monoclonal antibody;Carcinoembryonic antigen

 

数据来源: OVID

 

摘要:

PURPOSE:The aim of this study was to assess an immunotoxin, monoclonal antibody C27‐abrin A chain conjugate (MAAC), that might be effective in the treatment of colorectal carcinoma.METHODS:The immunotoxin was prepared by a specific monoclonal antibody against carcinoembryonic antigen (CEA), monoclonal antibody C27, linked toN‐succinimidyl‐3‐(2‐pyridyldithio)propionate and then coupled covalently to the toxic abrin‐A chain to synthesize MAAC. The therapeutic role of this immunotoxin in suppressing thein vitroandin vivogrowth of CEA‐secreting human colorectal cancer cells (LS174T) was assayed by methods of protein biosynthesis inhibition, cell colony proliferation, and treatment of tumor cells before and after inoculation in nude mice.RESULTS:We found that MAAC effectively suppressed the growth of LS174T in culture medium and completely eradicated cells in inoculated nude mice. In contrast, irrelevant immunotoxin antiferritin‐abrin A chain conjugate and isotype‐matched monoclonal immunoglobin (MOPC21IgG1)‐abrin A chain conjugate did not cause such effects. Thein vitrotoxicity was highly specific because the conjugate (MAAC) inhibitedde novoprotein biosynthesis, impeded growth, and caused death of cells possessing surface CEA determinants. The 50 percent inhibition dose values of the conjugate for colonogenic survival and for protein biosynthesis in LS174T cells were 0.09 μg/ml and 0.06 μg/ml, respectively. Colony survival was inhibited 96.3 percent after prolonged MAAC treatment. MAAC showed selective cytotoxicity; the inhibitory effect of MAAC to the CEA‐secreting LS174T cells over the CEA‐nonsecreting human embryonic kidney cells was 16‐fold.CONCLUSION:These results indicate that MAAC may be of benefit in therapy during or soon after resection of colorectal carcinoma or in patients who have micrometastasis.

 

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