Accession Number : ADA338689

Title :   Chimeric Enzyme/Prodrug Therapy as Novel Gene Therapy for Breast Cancer

Descriptive Note : Annual rept. 1 Aug 96-31 Jul 97

Corporate Author : PITTSBURGH UNIV PA

Personal Author(s) : Cooper, David L.

PDF Url : ADA338689

Report Date : AUG 1997

Pagination or Media Count : 13

Abstract : We have constructed a series of artificial chimeric genes each composed of a tumor-associated CD44 alternative splicing unit (ASU) which includes alternatively spliced exons and flanking introns and exons and the cytosine deaminase (CD) gene. The selective expression of active CD44/CD chimeric protein potentially enables tumor-specific killing via the RNA metabolism of alternative splicing following administration of the prodrug 5-FC. Insertion of the CD44 transmembrane region between 5'CD44 encoding exons and 3'-CD cDNA anchors the chimeric protein to the cell membrane while partitioning CD44 to the extracellular and CD to the intracellular compartments, respectively and results in no significant loss of CD enzymatic function. This modification makes it possible to introduce specific therapeutic receptor or antigen sites located outside the membrane allowing for recognition of cancer cells surviving the toxicity of the 5-FU anabolite.

Descriptors :   *ENZYMES, *GENES, *BREAST CANCER, MEMBRANES(BIOLOGY), PROTEINS, METABOLISM, DEOXYRIBONUCLEIC ACIDS, THERAPY, CELLS(BIOLOGY), RIBONUCLEIC ACIDS, ANTIGENS, SPLICES.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE