Targeting of Cytotoxic Conjugates to Kaposi's Sarcoma-Derived Cells

Abstract

We assayed the cytotoxicity of conjugates in which the plant toxin saporin (SAP) was linked to human basic fibroblast growth factor (bFGF) and urokinase-type plasminogen activator (uPA). Both bFGF and uPA play an important role in angiogenesis, and their cell surface receptors are expressed at high levels in cancer cells. The conjugates were tested on a Kaposi's sarcoma-derived cell line, IST-KS2, as a model of an actively proliferating component of Kaposi's sarcoma lesions which are highly vascularized. Both bFGF and uPA were very effective at targeting saporin to KS cells, leading to cell killing even at low concentrations of the conjugates. The bFGF–SAP and uPA–SAP mitotoxins were also highly toxic toward the permanent, endothelium-derived EAhy926 cell line. EAhy926 cells were very sensitive to two immunotoxins containing an anti-endothelium monoclonal antibody coupled to saporin or ricin A chain, whereas IST-KS2 cells were not affected by these conjugates, in agreement with immuno cytochemical observations.