Combinatorial Approach to the Isolation of Human Antibodies Fragments and Peptides to Breast Carcinomas

摘要

The focus of this research is to generate and characterize novel human antibody fragments (Fabs) and peptides that bind breast cancer cells. A combinatorial approach is being taken to generate immunoglobulin Fab that recognize a specific determinant on breast cancer cells including the breast cancer-associated Thomsen-Friedenreich (T) glycoantigen. In addition, human Fab and peptides will be generated from combinatorial libraries that bind breast cancer cells, irrespective of defined cell surface markers. The hypothesis that is implicit in these studies is that combinatorial approaches will provide Fab and peptides specific to either defined or ill-defined antigens present on breast cancer cells. The goals of this study are to: (1) generate human IgG Fab that bind specifically to the T antigen expressed on breast cancers from pre- existing Fab, (2) isolate Fab that bind ductal and lobular breast carcinoma cell lines from human combinatorial phage Fab display libraries, and (3) isolate peptides that bind breast carcinoma cell lines from combinatorial phage peptide display libraries. Results suggest phage libraries can yield Fab and scFv that bind to T antigen. Peptides and Fab that recognize lobular and ductal breast cancer cells are presently being sought.