Shiga-like toxin purges human lymphoma from bone marrow of severe combined immunodeficient mice.
Shiga-like toxin-1 (SLT-1) is a bacterial toxin that kills cells by inhibiting protein synthesis. SLT-1 is composed of one cytotoxic A-subunit and five B-subunits that bind to CD77, a cell-surface glycolipid. In the human hematopoietic system, CD77 expression is restricted to a subset of activated B cells and derived cancers. Here we report that SLT-1 treatment of murine bone marrow ex vivo effectively cures severe combined immunodeficient mice of a human B-cell lymphoma xenograft while sparing normal hematopoietic precursor cells. Flow cytometry results using fluorescein isothiocyanate-labeled SLT-1 B-subunit show the high prevalence of expression of SLT-1 receptors (CD77) in human non-Hodgkin's lymphomas, especially follicular lymphomas. These results suggest the use of SLT-1 for the purging of human bone marrow before autologous bone marrow transplant in the case of CD77+ B-cell lymphomas as just one of many possible uses.
LaCasse
E C
EC
Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Saleh
M T
MT
Patterson
B
B
Minden
M D
MD
Gariépy
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000378:metabolism / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011828:Radiation Chimera; D022622:Shiga Toxin 1; D013047:Specific Pathogen-Free Organisms; D014183:Transplantation, Heterologous; D014281:Trihexosylceramides / Q000378:metabolism*; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D022622:Shiga Toxin 1; D014281:Trihexosylceramides; C018549:globotriaosylceramide