Abstract
The heterodimer-forming leucine zippers Fos and Jun can efficiently mediate the formation of bispecific F(ab')2 when they are fused separately to two different Fab' fragments. This recombinant method can be used in conjunction with the humanization process to yield humanized bispecific F(ab')2. The potential immunogenicity of the leucine zippers can be eliminated by their removal using pepsin digestion. This method has been scaled up to produce hundreds of milligrams of a bispecific F(ab')2 that targets two subunits of the human IL-2 receptor.
MeSH terms
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Amino Acid Sequence
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Antibody Specificity
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Humans
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Immunoglobulin Fab Fragments / chemistry
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Immunoglobulin Fab Fragments / genetics
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Immunoglobulin Fab Fragments / immunology*
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Immunoglobulin Fab Fragments / metabolism
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Leucine Zippers* / drug effects
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Leucine Zippers* / genetics
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Molecular Sequence Data
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Oxidation-Reduction
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Pepsin A / pharmacology
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Protein Conformation
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Proto-Oncogene Proteins c-fos / chemistry
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / metabolism*
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Proto-Oncogene Proteins c-jun / chemistry
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Proto-Oncogene Proteins c-jun / genetics
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Proto-Oncogene Proteins c-jun / metabolism*
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Receptors, Interleukin-2 / immunology*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / immunology*
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Recombinant Fusion Proteins / metabolism
Substances
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Immunoglobulin Fab Fragments
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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Receptors, Interleukin-2
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Recombinant Fusion Proteins
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Pepsin A