Alpha(1,3) Galactosyltransferase Gene Therapy for Breast Cancer
Abstract
Alpha(1,3)galactosyl epitopes (alpha Gal) expressed on membrane glycoproteins and glycolipids are the major target of the human hyperacute rejection response observed when organs are transplanted from nonprimate donor species. Expression of the alpha(1,3)galactosyltransferase gene ALPHA(1,3)GT by breast cancer cells will lead to their direct in vivo destruction by anti-alpha Gal antibodies and complement, and boost the immune response to other tumor antigens. In vitro transduction of MCF-7, and T47D human breast cancer cells with an HSV amplicon vector resulted in expression of the suicide gene as detected by specific binding of labeled IB-4 isolectin. Transduced breast cancer cells were susceptible to antibody and complement-mediated cyolysis as demonstrated in serum killing as says with 50% human serum. The a(1,3)GT knockout mouse is analogous to humans in terms of expression of alpha Gal epitopes. A syngeneic murine breast cancer cell line form a(1,3)GT knockout mice has been produced by chemical induction (BR340) that is being used to demonstrate protective immunity when cells are ex vivo transduced and implanted into alpha Gal stimulated knockout mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418562
Entities
People
- Charles J. Link Jr