Expression of Diphtheria Toxin A-Chain in Mature B-Cells: A Potential Approach to Therapy of B-Lymphoid Malignancy
| العنوان: | Expression of Diphtheria Toxin A-Chain in Mature B-Cells: A Potential Approach to Therapy of B-Lymphoid Malignancy |
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| المؤلفون: | L. Michael Glode, Françoise Maxwell, Ian H. Maxwell |
| المصدر: | Leukemia & Lymphoma. 7:457-462 |
| بيانات النشر: | Informa UK Limited, 1992. |
| سنة النشر: | 1992 |
| مصطلحات موضوعية: | Diphtheria toxin, B-Lymphocytes, Cancer Research, Lymphoma, B-Cell, Genes, Immunoglobulin, Intron, Genetic Therapy, Hematology, Transfection, Biology, Molecular biology, Peptide Fragments, Immunoglobulin kappa-Chains, Mice, Exon, Oncology, Regulatory sequence, biology.protein, Animals, Diphtheria Toxin, Antibody, Enhancer, Gene, Plasmids |
| الوصف: | Specifically targeted expression of a toxin gene potentially represents a novel approach to cancer therapy. With a view to the ablation of B-cell malignancies, we have constructed a plasmid, designated pTHA71, which expresses the A-chain of diphtheria toxin (DT-A) with high efficiency and specificity in transfected, mature B-lymphoid cells. The construction incorporated immunoglobulin (Ig) kappa light chain gene regulatory sequences, including a kappa promoter, small intron, partial constant region exon, and 3'-flanking sequence (but lacking a known enhancer). These sequences conferred substantially more efficient expression of DT-A in mature B-cells than was seen from constructs that included only Ig promoters and enhancers. When transfected into the 70Z/3 murine pre-B-cell line, pTHA71 was only expressed efficiently if the cells were induced to express their endogenous, rearranged Ig kappa gene by prior exposure to lipopolysaccharide. The insertion of the enhancer from the Ig kappa large intron into pTHA71, generating pTHA81, did not markedly influence the level of DT-A expression in 70Z/3 cells. The observed absence of expression in pre-B-cells suggests that DT-A constructs similar to pTHA71 might be used for the therapeutic ablation of malignant B-cells of mature stages, while sparing normal progenitor cells. |
| تدمد: | 1029-2403 1042-8194 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd4f428ca384b197726e64b2e5cb59f3 https://doi.org/10.3109/10428199209049802 |
| رقم الأكسشن: | edsair.doi.dedup.....cd4f428ca384b197726e64b2e5cb59f3 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 10292403 10428194 |
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