B7-1 (CD80) as target for immunotoxin therapy for Hodgkin's disease
| Autor: | Letizia Polito, Andrea Bolognesi, H. Bohlen, M. de Boer, Henderikus G. Otten, R.A. de Weger, M. van Vliet, G. C. De Gast, WC Vooijs, A. J. van Dijk |
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| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
Neutrophils Biology Immunotoxin Tumor Cells Cultured medicine Humans Tissue Distribution Progenitor cell Cytotoxicity Antibodies Monoclonal Cytotoxicity Tests Immunologic Hematopoietic Stem Cells Hodgkin Disease Immunohistochemistry Molecular biology Clone Cells Raji cell Endothelial stem cell Haematopoiesis Treatment Outcome medicine.anatomical_structure Oncology Cell culture Immunology B7-1 Antigen Leukocytes Mononuclear Immunotherapy Lymph Nodes Bone marrow Research Article |
| Zdroj: | Scopus-Elsevier British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.1997.528 |
| Popis: | In this preclinical study, the potential applicability of an anti-B7-1 immunotoxin (IT) for the treatment of Hodgkin's disease (HD) was investigated. Immunohistochemical analysis demonstrated strong expression of B7-1 on Hodgkin and Reed-Sternberg (R-S) cells and clear expression on dendritic cells, macrophages and some B-cells in tissues, but not on other tissue cells. Flow cytometric analysis demonstrated that B7-1 was expressed on a few monocytes, but not on CD34+ cells from bone marrow, resting T- or B-cells from peripheral blood or epithelial and endothelial cell lines. An anti-B7-1 immunotoxin containing the anti-B7-1 monoclonal antibody (MAb) B7-24 and saporin as toxin moiety was constructed and showed an affinity similar to that shown by the native MAb. It exhibited strong cytotoxicity against the B7-1+ B-cell line Raji (IC50 10(-11) M), R-S cell lines HDLM2, KM/H2 and L428 and also against a B7-1-transfected epithelial cell line, A431, whose parental line lacks expression of B7-1. In clonogenic assays with Raji cells or KM/H2 cells, a 3- or 4-log kill, respectively, was observed. No cytotoxicity was found against the B7-1- epithelial and endothelial cell lines or against haematopoietic progenitor cells. In conclusion, an anti-B7-1 immunotoxin was developed that had good cytotoxicity against R-S cell lines and that may be used in the elimination of R-S cells in vivo. A concomitant elimination of activated antigen-presenting cells may avoid development of antitoxin and anti-mouse Ig responses and allow repeated administration. Images Figure 1 |
| Databáze: | OpenAIRE |
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