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 erbB-2 (Her2/neu), an oncogene product overexpressed by 30-50% of breast carcinomas, and the extracellular domain of B7.2 (CD86). This fusion protein was expressed and purified from Pichia pastoris, shown to retain binding activity to both counter receptors, erbB-2 and CD28, and shown to provide the costimulatory signal to T cells through CD28. Thus, our fusion protein was shown capable of targeting erbB-2 postive tumor cells and delivering a CD28 specific T cell costimulatory signal. Further studies should characterize the fusion protein in erbB-2 tumor bearing mice for in vivo tumor targeting, biodistribution, and efficacy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA371274
Entities
People
- James D. Marks
- Keith W. Marshall
Organizations
- University of California, San Francisco