Growth suppression of human colorectal carcinoma in nude mice by monoclonal antibody C27-abrin A chain conjugate |
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| Authors: | Lai-Chen Tsai BS Yung-Liang Chen MS Chung Lee PhD Horng-Min Chen MS Zo-Nan Chang BS Mei-Whey Hung BS Pei-Ling Chao MS Jung-Yaw Lin PhD |
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| Institution: | (1) Department of Medical Research, Veterans General Hospital-Taipei, Taipei, Taiwan;(2) School of Medical Technology, National Yang-Ming University, Taipei, Taiwan;(3) Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan;(4) Department of Urology, Northwestern University Medical School, Chicago, Illinois;(5) Laboratory of Clinical Immunology, Department of Medical Research, VGH-Taipei, 11217 Taipei, Taiwan |
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| Abstract: | 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 vitro andin vivo growth 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 vitro toxicity was highly specific because the conjugate (MAAC) inhibitedde novo protein 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  g/ml and 0.06 g/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.Supported by a grant from the National Science Council and the Veterans General Hospital-Taipei, Taipei, Taiwan. |
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| Keywords: | Colorectal carcinoma Abrin A chain immunoconjugate Monoclonal antibody Carcinoembryonic antigen |
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