| 摘要 |
PCT No. PCT/IB96/01032 Sec. 371 Date Apr. 27, 1998 Sec. 102(e) Date Apr. 27, 1998 PCT Filed Jun. 28, 1996 PCT Pub. No. WO97/02479 PCT Pub. Date Jan. 23, 1997Human monoclonal anti-tumor antibodies are isolated from fusion phage single-chain Fv and VH antibody libraries constructed from the peripheral blood lymphocytes of immunized cancer patients. Antibodies that bind to tumor cells of the same kind as the patient's are selected, and antibodies that also bind to a human normal cell type are removed. The remaining fusion phage antibodies are cloned and then are tested for binding to at least two normal human cell types. Antibodies that fail to bind to the normal cells are further tested for binding to a panel of tumor cells, typically including the original tumor type and several related and unrelated tumors. Human monoclonal antibodies that bind specifically to the original tumor or also to some other tumors, or that bind to the original tumor and cells from the same developmental lineage, are obtained and sequenced. The selected antibodies can be used to design molecules which are potentially useful for various diagnostic and therapeutic purposes. The single-chain Fv and VH libraries from cancer patients are also being used to select antibodies against other targets, such as endothelial cells, which have diagnostic and clinical applications.
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