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Generation of a recombinant mouse‐human chimaeric monoclonal antibody directed against human carcinoembryonic antigen
Author(s) -
Hardman Norman,
Gill L. Lee,
de Winter Ronald F. J.,
Wagner Kathrin,
Hollis Melvyn,
Businger Felix,
Ammaturo Domenico,
Buchegger Franz,
Mach JeanPierre,
Heusser Christoph
Publication year - 1989
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910440308
Subject(s) - carcinoembryonic antigen , monoclonal antibody , recombinant dna , antigen , antibody , biology , microbiology and biotechnology , medicine , virology , immunology , cancer , biochemistry , genetics , gene
A procedure was devised for the identification and specific cloning of functionally rearranged variable region immunoglobulin (Ig) gene segments from genomic DNA of a murine hybridoma cell line which produces a high‐affinity monoclonal antibody (MAb) directed against human carcinoembryonic antigen (CEA). The cloned, functionally‐rearranged murine Ig H‐chain and L‐chain variable region gene segments were incorporated into plasmid vectors capable of directing the expression of a chimaeric mouse‐human antibody molecule with human (Y4,K) constant region sequences. Expression plasmids were transfected into a mouse myeloma cell line by electro‐poration and transfectomas secreting functional chimaeric antibody selected. Chimaeric antibody generated by transfectomas was analysed and shown to compete effectively with its murine counterpart for binding to the CEA epitope, and to have an equivalent antigen‐binding affinity. This anti‐CEA recombinant antibody should find application in in vivo diagnosis by immunoscintigraphy of human colonic carcinoma, and possibly also in therapy of the disease, overcoming some of the difficulties associated with the repeated use of non‐human immunoglobulins in human patients.