Engineering Bispecific Antibodies that Target ErbB-2 on Breast Cancer Cells
Abstract
The purpose of this project is twofold. First, to construct novel bispecific antibodies that can be expressed as a single-chain in E. coli.. Second, to develop an in vivo animal model, using a TCR transgenic/RAG(-/-) strain of mice, for evaluating agents that will redirect the activity of T cells. In the past year, the following specific aims toward these goals were accomplished: (1) Two different scFv2 antibodies were expressed as inclusion bodies in E. coli, purified and tested in vitro; because these showed less than optimal activity (>10 nM), one of the scFv2 genes was expressed in a yeast secretion system; (2) Agents that will activate T cells from the TCR/RAG mice were examined; both anti CD3 and anti CD28 antibodies and a specific peptide were shown to stimulate proliferation; the peptide was used in vivo and optimal parameters for CTL activation were determined. (3) An alternative bispecific agent, folate anti-TCR antibody, for targeting high affinity folate receptors on tumor cells was further developed; these agents target tumors in vitro at very low doses (<0.1 nM). (4) Folate antibody agents were used in TCR/RAG mice to evaluate parameters for efficient in vivo targeting of human tumors. This animal model will allow further testing of these and other bispecific agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1997
- Accession Number
- ADA340988
Entities
People
- David M. Kranz
Organizations
- University of Illinois Urbana–Champaign