Targeting of Cytolytic T-cells for Breast Cancer Therapy Using Novel-Fusion Proteins
Annual rept 1 Aug 96-31 Jul 97
CALIFORNIA UNIV SAN FRANCISCO
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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 Her2neu, 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.
- Medicine and Medical Research