Selective cytotoxicity of a ricin A-chain-anti-carcinoembryonic antigen antibody conjugate for a human colon adenocarcinoma cell line.
Ricin A-chain, the toxic subunit of the potent plant toxin ricin, has been isolated by affinity chromatography and conjugated via a disulfide linkage to affinity-purified goat anti-carcinoembryonic antigen (CEA) antibody. Such conjugates retained the integrity of their antibody-combining site, as demonstrated by the ability to displace 125I-labeled anti-CEA antibody bound to CEA-positive cell lines. In addition, such conjugates retained A-chain activity, producing inhibition of [14C]leucine incorporation into a CEA-negative G-361 human melanoma cell line at concentrations similar to those of unconjugated A-chain. However, these conjugates were 40 times as potent in the inhibiton of [14C]leucine incorporation in the CEA-bearing WiDr human adenocarcinoma cell line as A-chain alone or as an unreacted mixture of A-chain and specific antibody. Such toxicity could be blocked by preincubation of the conjugate with fluid-phase CEA. Complete inhibition of [14C]leucine incorporation as well as inhibition of cellular proliferation by the conjugate was seen at 50 nM concentration. Conjugates that combine the determinant specificity of an antibody with the toxicity of ricin A-chain may show promise as selective cytotoxins for cells bearing CEA.
D000230:Adenocarcinoma / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology; D000918:Antibody Specificity; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002455:Cell Division; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008970:Molecular Weight; D012276:Ricin / Q000276:immunology* / Q000302:isolation & purification
D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen; D012276:Ricin; D007930:Leucine