The use of Shiga-like toxin 1 in cancer therapy

Abstract

The ribosome-inactivating protein, Shiga-like toxin-1 (SLT-1, SLT-I, Verotoxin 1, VT1) targets cells that express the glycolipid globotriaosylceramide (CD77) on their surface. The frequent occurrence of SLT-1 receptors on tumor cells derived from patients with hematological cancers (follicular lymphoma, multiple myeloma, chronic lymphocytic leukemia) and their absence on human CD34(+) hematopoietic stem cells suggest the ex vivo use of Shiga-like toxin-1 in purging CD77(+) tumor cells from autologous stem cell transplants. SLT-1 receptors are also commonly expressed on breast cancer, ovarian cancer and astrocytoma cells. In particular, the sensitivity of astrocytoma cell lines to this toxin provides an opportunity for using SLT-1 in vivo in the context of treating patients afflicted by this common form of brain tumor. Finally, the known structural features of SLT-1 allow one to contemplate altering its receptor specificity in an effort to target CD77(-) tumor cell populations.