Shiga-like toxin-1 receptor on human breast cancer, lymphoma, and myeloma and absence from CD34(+) hematopoietic stem cells: Implications for ex vivotumor purging and autologous stem cell transplantation

The ribosome-inactivating protein, Shiga-like toxin-1 (SLT-1), targets cell s that express the glycolipid globotriaosylceramide (CD77) on their surface . CD77 and/or SLT-1 binding was detected by Row cytometry and immunocytoche mistry on lymphoma and breast cancer cells recovered from biopsies of prima ry human cancers as well as on B cells or plasma cells present in blood/bon e marrow samples of multiple myeloma patients. Breast cancer cell lines als o expressed receptors for the toxin and were sensitive to SLT-1, Treatment of primary B lymphoma, B-cell chronic lymphocytic leukemia, and myeloma B o r plasma cells with SLT-1-depleted malignant B cells by 3- to 28-fold, as m easured by flow cytometry, Depletion of myeloma plasma cells was confirmed using a cellular limiting dilution assay followed by reverse transcriptase- polymerase chain reaction analysis of clonotypic IgH transcripts, which sho wed a greater than 3 log reduction in clonotypic myeloma cells after SLT-1 treatment, Receptors for the toxin were not detected on human CD34(+) hemat opoietic progenitor cells (HPC), HPC were pretreated with a concentration o f SLT-1 known to purge primary malignant B cells and cultured for 6 days, T he number of HPC was comparable in toxin-treated and untreated cultures. HP C were functionally intact as well. Colony-forming units (CFU) were present at an identical frequency in untreated and SLT-1 pretreated cultures, conf irming that CFU escape SLT-1 toxicity. The results suggest the ex vivo use of SLT-1 in purging SLT-1 receptor-expressing malignant cells from autologo us stem cell grafts of breast cancer, lymphoma, and myeloma patients. (C) 1 999 by The American Society of Hematology.