Kinetic comparison of ricin immunotoxins: biricin conjugate has potentiated cytotoxicity.
The plant toxin ricin was chemically coupled to an anti-Thy-1.1 antibody, and the resultant conjugates were fractionated by gel filtration. The cytotoxicity of the conjugate possessing two ricin molecules per immunoglobulin, yielding a first-order inactivation rate of protein synthesis of -0.4 log/h at 200 ng/mL, was well above that expected just from the increase in ricin per unit mass of conjugate, when compared to a conjugate possessing only one ricin per immunoglobulin. On a conjugate molar scale the biricin immunotoxin was determined to be 8 times more potent than the monoricin conjugate; thus, relative to the number of ricin molecules, the coupling of a second ricin to the immunoglobulin quadrupled the observed potency. The concentration of immunotoxin and the resultant inactivation rates of protein synthesis were found to be related through a power function. Additionally, the inactivation kinetics of these conjugates were found to be similar to those of native ricin.
D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D000922:Immunotoxins / Q000302:isolation & purification / Q000633:toxicity*; D007457:Iodine Radioisotopes; D007700:Kinetics; D051379:Mice; D008806:Mice, Inbred AKR; D014176:Protein Biosynthesis; D012276:Ricin / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D012276:Ricin