Accession Number : ADA333270

Title :   Targeting of Cytolytic T-cells for Breast Cancer Therapy Using Novel-Fusion Proteins

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

Corporate Author : CALIFORNIA UNIV SAN FRANCISCO

Personal Author(s) : Marks, James D. ; Marshall, Keith W.

PDF Url : ADA333270

Report Date : AUG 1997

Pagination or Media Count : 21

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.

Descriptors :   *CYTOCHEMISTRY, *BREAST CANCER, PEPTIDES, GLYCOPROTEINS, NEOPLASMS, THERAPY, ANTIBODIES, IMMUNOLOGY, T LYMPHOCYTES, CELLS(BIOLOGY), ANTIGENS.

Subject Categories : Biochemistry
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE