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Immunological engineering for generation of human therapeutic antibodies

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Summary: A method for the generation of high functional variability in antibody libraries has been developed. One part of the method is based on a previously conceived concept of library construction that was initiated at the Department of Immunotechnology at Lund University. Application of the method has resulted in a large antibody library that is displayed on phage. Several high affinity antibodies have been selected from the library. The other part of the method utilizes a novel selection technology called SAP that allows selection of antibodies on binding parameters. This selection technology utilizes phage that have been made non-infectious through deletion of protein 3, the phage component normally mediating infection of bacteria. Phage that display specific antibodies can now be allowed to infect through binding to a fusion protein comprising the antigenic epitome of choice and the N-terminal parts of protein 3. The method used for creation of variability is very efficient and its application has resulted in a large human antibody fragment library. The selection method called SAP allows for efficient selection of i.e. high affinity antibodies. The two components can be used in concert or other selection technologies may be employed should they be preferred.

Verwertbare Ergebnisse

23379A set of human single chain antibody fragments against human MUC 1 has been developed using recombinant and cellular technologies. The antibodies react with synthetic MUC-1 peptides as well as native epitopes expressed on human tumour cells. The affinities have been measured to range from 10 power 6 to 10 power 9 M power -1.

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