Engineering Bispecific Antibodies that Target ErbB-2 on Breast Cancer Cells

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. I...

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Bibliographic Details
Main Author: Kranz, David M
Format: Report
Language:English
Subjects:
Anatomy and Physiology
ANTIBODIES
Biochemistry
BISPECIFIC ANTIBODIES
BREAST CANCER
CELLS(BIOLOGY)
CYTOTOXICITY
CYTOTOXINS
ERBB-2
ESCHERICHIA COLI
GENES
HUMANS
IMMUNITY
IMMUNOTHERAPY
IN VITRO ANALYSIS
IN VIVO ANALYSIS
Medicine and Medical Research
NEOPLASMS
PEPTIDES
SCFV2 ANTIBODIES
T LYMPHOCYTES
YEASTS
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Summary: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 (