GROWTH SUPPRESSION OF HUMAN COLORECTAL-CARCINOMA IN NUDE-MICE BY MONOCLONAL-ANTIBODY C27-ABRIN A-CHAIN CONJUGATE

PURPOSE: The aim of this study was to assess an immunotoxin, monoclona l antibody C27-abrin A chain conjugate (MAAC), that might be effective in the treatment of colorectal carcinoma. METHODS: The immunotoxin wa s prepared by a specific monoclonal antibody against carcinoembryonic antigen (CEA), monoclonal antibody C27, linked to N-succinimidyl-3(2-p yridyldithio)propionate and then coupled covalently to the toxic abrin -A chain to synthesize MAAC. The therapeutic role of this immunotoxin in suppressing the in vitro and in vivo growth of CEA-secreting human colorectal cancer cells (LS174T) was assayed by methods of protein bio synthesis inhibition, cell colony proliferation, and treatment of tumo r cells before and after inoculation in nude mice. RESULTS: We found t hat 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 isoty pe-matched monoclonal immunoglobin (MOPC21IgG1)-abrin A chain conjugat e did not cause such effects. The in vitro toxicity was highly specifi c because the conjugate (MAAC) inhibited de novo protein biosynthesis, impeded growth, and caused death of cells possessing surface CEA dete rminants. The 50 percent inhibition dose values of the conjugate for c olonogenic survival and for protein biosynthesis in LS174T cells were 0.09 mu g/ml and 0.06 mu g/ml, respectively. Colony survival was inhib ited 96.3 percent after prolonged MAAC treatment. MAAC showed selectiv e cytotoxicity; the inhibitory effect of MAAC to the CEA-secreting LS1 74T cells over the CEA-nonsecreting human embryonic kidney cells was 1 6-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.