Selection of Human Antibody Fragments which Bind Novel Breast Tumor Antigens
Abstract
A major goal of cancer research has been to identify tumor antigens which are qualitatively or quantitatively different from normal cells. The presence of such antigens could be detected by monoclonal antibodies that would form the basis of diagnostic tests and therapeutic agents. For this project, we developed novel technology, antibody phage display, to produce a new generation of tumor specific antibodies. We produced a library of human antibodies from which we can isolate panels of monoclonal antibodies to any purified antigen within 2 weeks. Methodologies have been developed to increase antibody affinity to values not previously achievable. Finally, we have developed methodologies which permit direct selection of libraries on tumor cells for the purpose of generating antibodies with desirable functional properties, such as endocytosis and growth inhibition. A panel of antibodies have been isolated which are breast tumor cell specific and a method has been developed where the antibody can be used to identify the receptor bound. We have applied these technologies to produce several human antibodies that bind the ErbB2 receptor overexpressed in one third of breast cancers. With collaborators at UCSF, we have used these antibodies to target doxorubicin containing liposomes, which can cure tumors in mice. The National Cancer Institute Decision Network is supporting further pre-clinical development for anticipated clinical trials for breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA382534
Entities
People
- James D. Marks
Organizations
- University of California, San Francisco