Sensitivity of target cells to immunotoxins: possible role of cell-surface antigens

In this paper, we describe the activity of conjugates constituted of monoclonal antibodies chemically coupled to ricin and the ricin A-chain-like toxin gelonin. Several antibody-toxin conjugates (immunotoxins) were assayed against a Thy 1.2+ and Lyt 2.2+ T-cell line. Anti-Thy 1.2-gelonin and anti-Lyt 2.2-ricin immunotoxins (IT) had a good cytotoxic activity against target cells, whereas anti-Lyt 2.2-gelonin showed weak or no cytotoxicity. An anti-Lyt 2.2-gelonin IT displayed detectable cytotoxicity only when cells were pretreated with ammonium chloride. IT binding activity was very similar for anti-Thy 1.2 and anti-Lyt 2.2 IT, and surface antigen density was of the same order of magnitude for Thy 1.2 and Lyt 2.2 antigens. Our results suggest that intrinsic properties of the surface target antigen are able to influence the IT cytotoxic efficacy.