Shiga-like toxin purges human lymphoma from bone marrow of severe combined immunodeficient mice

Blood. 1996 Sep 1;88(5):1561-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Bacterial Toxins / metabolism
  • Bacterial Toxins / therapeutic use*
  • Bone Marrow / drug effects*
  • Bone Marrow / pathology
  • Bone Marrow Purging*
  • Bone Marrow Transplantation*
  • Burkitt Lymphoma / drug therapy*
  • Burkitt Lymphoma / pathology
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Neoplasm Transplantation
  • Radiation Chimera
  • Shiga Toxin 1
  • Specific Pathogen-Free Organisms
  • Transplantation, Heterologous
  • Trihexosylceramides / metabolism*
  • Tumor Stem Cell Assay

Substances

  • Antineoplastic Agents
  • Bacterial Toxins
  • Shiga Toxin 1
  • Trihexosylceramides
  • globotriaosylceramide