Selection of Human Antibody Fragments which Bind Novel Breast Tumor Antigens.
Annual rept. 15 Aug 94-14 Aug 95,
CALIFORNIA UNIV SAN FRANCISCO
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This report describes the results of year 1 of a 4 year grant to develop high affinity human antibody fragments to novel breast tumor antigens. To produce human antibody fragments which bind to novel tumor antigens, we have created a very large 7.0 x member single chain Fv scFv phage antibody library. This library contains multiple antibody fragments to every antigen used for selection. In future work, this library will be selected on breast tumor cell lines to isolate tumor specific antibody fragments. Methodology has also been developed to increase antibody fragment affinity in vitro. We have determined how to optimally create, select, elute and screen mutant phage antibodies for higher affinity binding. These techniques have been applied to increase the affinity of an scFv C6.5 which binds to the breast tumor antigen c-erbB-2. The affinity of C6.5 was increased 100 fold to a Kd of 1.6 x 10-10 M, making it the highest affinity human antibody ever produced to a tumor antigen. Increased affinity results in greater quantitative delivery of scFv to human tumor xenografts.
- Medicine and Medical Research
- Anatomy and Physiology