Targeting of Cytolytic T-cells for Breast Cancer Therapy Using Novel-Fusion Proteins
Abstract
The provision of the T cell costimulatory molecule B7 to tumor cells can be an effective means of triggering a tumor specific cytolytic T cells response. One way to provide B7 to tumor cells would be to couple an anti-tumor antibody either directly to B7 or to an antibody to the B7 counterreceptor on T cells, CD28. To this end, a fusion protein has been developed which incorporates a single chain antibody fragment (scFv) to c-erbB-2 (Her2/neu), an oncogene product overexpressed by 30-50% of breast carcinomas, and the extracellular domain of B7-2 (CD86). Experiments are currently underway to determine if the fusion protein can bind to c-erbB-2 and CD28, and also to measure its ability to activate T-cells. In addition, single chain antibody fragments are currently being selected, using a phage display scFv library, which are specific for the T cell costimulatory receptor molecule CD28. Anti-CD28 scFv with a range of affinities will be isolated and the role of affinity and differential binding to T cell costimulatory receptors will be determined to identify their importance in the biology of T cell activation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1997
- Accession Number
- ADA333270
Entities
People
- James D. Marks
- Keith W. Marshall
Organizations
- University of California, San Francisco