The use of Shiga-like toxin 1 in cancer therapy.
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.
Gariépy
J
J
Department of Medical Biophysics, University of Toronto, University Health Network, 610 University Ave., Toronto, Ont., Canada, M5G 2M9. gariepy@oci.utoronto.ca
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000188:drug therapy*; D022622:Shiga Toxin 1 / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D019172:Transplantation Conditioning; D014281:Trihexosylceramides / Q000378:metabolism
D000970:Antineoplastic Agents; D022622:Shiga Toxin 1; D014281:Trihexosylceramides; C018549:globotriaosylceramide