Accession Number:

ADA371274

Title:

Targeting of Cytolytic T-Cells for Breast Cancer Therapy Using Novel-Fusion Proteins

Descriptive Note:

Annual rept. 1 Aug 96-31 Jul 99

Corporate Author:

CALIFORNIA UNIV SAN FRANCISCO

Personal Author(s):

Report Date:

1999-07-01

Pagination or Media Count:

47.0

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 Her2neu, 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.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE