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Therapeutic human antibodies derived from PCR amplification of B-cell variable regions.
- Source :
-
Immunological reviews [Immunol Rev] 1992 Dec; Vol. 130, pp. 69-85. - Publication Year :
- 1992
-
Abstract
- Despite advances in the in vitro immunization of human B cells (Borrebaeck et al. 1988) and the development of immunodeficient mice (McCune et al. 1988) for the reconstitution of the human immune system ex vivo, immortalization of antigen-specific human B cells remains the limiting step in the generation of human monoclonal antibodies. Typically this is performed with the aid of Epstein-Barr virus transformation followed by subcloning, confirmation of antigen binding and hybridization of the B lymphoblasts to a suitable fusion partner such as GLI-H7. This general approach is effective and widely used; however, it is time-consuming with erratic results. These were the immediate reasons we and others devised methods to directly obtain the variable regions from small numbers of human B cells (Larrick et al. 1987). The success of the PCR-based approach is illustrated above. In the present studies we successfully captured and stably produced antibodies from the V regions of two potent human anti-tetanus antibodies secreted by heteromyelomas that were too unstable for scale-up production. Although further preclinical evaluation of these antibodies is in progress, results to date indicate that the recombinant antibodies produced in myeloma-based cell lines or CHO cells are equivalent in binding specificity and activity to the native heteromyeloma-derived antibodies. Recent studies from this laboratory indicate that effective anti-tetanus protection will require a cocktail of anti-tetanus antibodies. Details of this work will be the subject of a future communication (Lang et al., in preparation).
- Subjects :
- Amino Acid Sequence
Animals
Antibodies, Bacterial genetics
Antibodies, Bacterial therapeutic use
Antibodies, Monoclonal genetics
Antibodies, Monoclonal immunology
Antibodies, Monoclonal therapeutic use
Base Sequence
CHO Cells
Cell Line, Transformed
Cricetinae
DNA genetics
Enzyme-Linked Immunosorbent Assay
Humans
Hybridomas immunology
Immunoglobulin Heavy Chains genetics
Immunoglobulin Heavy Chains immunology
Immunoglobulin Variable Region immunology
Mice
Molecular Sequence Data
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins therapeutic use
Transfection
Antibodies, Bacterial biosynthesis
Antibodies, Monoclonal biosynthesis
Genes, Immunoglobulin
Immunoglobulin Variable Region genetics
Polymerase Chain Reaction
Recombinant Fusion Proteins biosynthesis
Tetanus Toxoid immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0105-2896
- Volume :
- 130
- Database :
- MEDLINE
- Journal :
- Immunological reviews
- Publication Type :
- Academic Journal
- Accession number :
- 1286873
- Full Text :
- https://doi.org/10.1111/j.1600-065x.1992.tb01521.x