Protein-Engineered Radiometal Chelates for Immunotherapy of Breast Cancer

Abstract

The objective of this project is to genetically engineer a radiometal binding site in a human antibody constant region, for eventual use in tumor radioimmunotherapy. Our initial design was based on molecular modeling and used a humanized antibody Fab fragment expressed in E. coli. The engineered binding site, consisting of 5 point mutations in the human Ck domain, destabilized the recombinant protein, leading to proteolysis. We have attempted to address this problem by using expedited isolation procedures, modifying the binding site design, and expressing the protein within protease-negative host strains.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 1998
Accession Number
ADA360809

Entities

People

  • Jefferson Foote

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Antibodies
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Chemical Compounds
  • Chemistry
  • Immunoglobulins
  • Immunotherapy
  • Laboratory Animals
  • Low Temperature
  • Macromolecules
  • Materials
  • Molecules
  • Mutations
  • Neoplasms
  • Proteins

Fields of Study

  • Biology

Readers

  • Molecular and Cellular Biochemistry
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech