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The conjugate Rituximab/saporin-S6 completely inhibits clonogenic growth of CD20-expressing cells and produces a synergistic toxic effect with Fludarabine.
- Source :
-
Leukemia [Leukemia] 2004 Jul; Vol. 18 (7), pp. 1215-22. - Publication Year :
- 2004
-
Abstract
- Immunotoxins are chimeric proteins consisting of a toxin coupled to an antibody. To date, several clinical trials have been conducted, and some are still ongoing, to evaluate their anti-tumor efficacy. In this view, we chemically constructed an anti-CD20 immunotoxin with the mAb Rituximab and the type 1 ribosome-inactivating protein (RIP) saporin-S6, designed for B cells non-Hodgkin's lymphoma (NHL) therapy. This immunotoxin showed a specific cytotoxicity for the CD20+ cell lines Raji and D430B, evidenced by inhibition of protein synthesis, evaluation of apoptosis and clonogenic assay. Upon conjugation, saporin-S6 increased its toxicity on target cells by at least 2 logs, with IC(50) values of 0.1-0.3 nM. The percentage of AnnexinV+ cells was over 95% in both cell lines treated with 10 nM immunotoxin. A complete elimination of Raji clones was reached with the 10 nM immunotoxin, whereas a mixture of free RIP and mAb gave about 90% of clonogenic growth. Rituximab/saporin-S6, at 10 nM concentration, also induced apoptosis in 80% of lymphoma cells from NHL patients. Moreover, sensitivity of Raji to Rituximab/saporin-S6 was augmented when cells were coincubated with Fludarabine. The synergistic toxic effect of the two drugs led to a total elimination of the neoplastic population.
- Subjects :
- Antibodies, Monoclonal, Murine-Derived
Antigens, CD20
Antineoplastic Combined Chemotherapy Protocols pharmacology
B-Lymphocytes immunology
B-Lymphocytes pathology
Cell Division drug effects
Cell Line, Transformed
Clone Cells drug effects
Clone Cells pathology
Drug Synergism
Humans
Ribosome Inactivating Proteins, Type 1
Rituximab
Saporins
Tumor Cells, Cultured
Antibodies, Monoclonal pharmacology
B-Lymphocytes drug effects
Immunotoxins pharmacology
N-Glycosyl Hydrolases pharmacology
Plant Proteins pharmacology
Vidarabine analogs & derivatives
Vidarabine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0887-6924
- Volume :
- 18
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Leukemia
- Publication Type :
- Academic Journal
- Accession number :
- 15103391
- Full Text :
- https://doi.org/10.1038/sj.leu.2403378