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Expression of the Diphtheria Toxin A-Chain Coding Sequence under the Control of Promoters and Enhancers from Immunoglobulin Genes as a Means of Directing Toxicity to B-Lymphoid Cells¹

Division of Medical Oncology, University of Colorado Health Sciences Center, Denver, Colorado 80262

Previous resutls have shown that cells can be killed by the expression of an introduced gene encoding diphtheria toxin A-fragment (DT-A) and that killing can be targeted using tissue-specific transcriptional regulatory elements. Here, we describe expression plasmids containing the DT-A gene linked with promoters and enhancers from immunoglobulin heavy chain or -light chain genes. When these plasmids were transfected into cultured cells, DT-A was expressed in B-lymphoid cells but not detectably in HeLa cells or fibroblasts. A high specificity for B-cells was confirmed by assaying for luciferase reporter gene expression from a plasmid containing an analogous combination of immunoglobulin heavy chain regulatory elements. A plasmid containing an immunoglobulin- promoter and enhancer was substantially less active in expressing DT-A in a pre-B-cell line than in B-lymphoma cells, suggesting the possibility of targeting DT-A expression to mature, malignant B-cells while sparing normal B-cell progenitors. By means of viral delivery vehicles, the constructs described might be applied in gene therapy for B cell leuke mias or lymphomas.

¹ Supported by NIH Grant CA42354 (I. H. M.) and by grants from the Cancer League of Colorado and the University of Colorado Cancer Research Foundation.

² To whom requests for reprints should be addressed, at Division of Medical Oncology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue B171, Denver, CO 80262.

Received 2/21/91. Accepted 6/ 6/91.

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