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, phage display, to produce a new generation of antibodies. We have 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 achievable previously. Finally, we have developed methodologies to select libraries directly on tumor cells for the purpose of generating antibodies with desirable functional properties, such as inhibition of cell growth or induction of apoptosis. Tumor cell specific antibodies have been isolated and are being used to identify the antigens to which they bind. This should result in the identification of novel tumor antigens. We have applied these technologies to produce a human antibody that targets 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 mice of tumors. 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, 1997
- Accession Number
- ADB236087
Entities
People
- James D. Marks
Organizations
- University of California, San Francisco