Abrogation of the non-specific toxicity of abrin conjugated to anti-lymphocyte globulin.

Abstract

A covalent conjugate of abrin and anti-human lymphocyte globulin (AHLG) was prepared in an endeavour to create a cytotoxic agent with specificity for human lymphoid cells. The AHLG--abrin conjugate was found to be around 10-fold better able to inhibit 3H-leucine uptake by the human lymphoblastoid cell line, Daudi, in tissue culture than was the control conjugate comprising abrin and normal IgG (nIgG). Both materials were less potent than native abrin. Galactose, which is known competitively to antagonize the binding of abrin to cells, strongly inhibited the toxicities of abrin and the nIgG--abrin conjugate whereas that of ALG--abrin was unimpaired. Thus, at least for Daudi cells in tissue culture, abrin can be made selectively toxic, by linkage to AHLG, towards cells bearing antigens to which the antibody moiety of the conjugate can attach.