The first constant domain (CH1 and CL) of an antibody used as heterodimerization domain for bispecific miniantibodies

@article{Mller1998TheFC,
  title={The first constant domain (CH1 and CL) of an antibody used as heterodimerization domain for bispecific miniantibodies},
  author={K M M{\"u}ller and Katja M. Arndt and Wolfgang Strittmatter and Andreas Pl{\"u}ckthun},
  journal={FEBS Letters},
  year={1998},
  volume={422}
}
Bispecific miniantibodies were constructed by genetically fusing the CH1 domain of an IgG1 to the C‐terminus of a single‐chain Fv fragment (scFv‐425), specific for the EGF receptor, and fusing the CL domain of a kappa light chain to the C‐terminus of a scFv specific for CD2 (scFv‐M1). An efficient dicistronic gene arrangement for functional expression in Escherichia coli was constructed. Immunoblots demonstrated correct domain assembly and the formation of the natural CH1‐CL disulfide bridge… 
View on Wiley
febs.onlinelibrary.wiley.com
77 Citations
Highly Influential Citations
3
Background Citations
22
Methods Citations
12

77 Citations

Citation Type

Citation Type

A dimeric bispecific miniantibody combines two specificities with avidity
TLDR
The dimeric bispecific (DiBi) miniantibody preserves the natural avidity of antibodies in a very small‐sized molecule of only 120 kDa.
Fab Chains As an Efficient Heterodimerization Scaffold for the Production of Recombinant Bispecific and Trispecific Antibody Derivatives1
TLDR
The use of the disulfide-stabilized L:Fd heterodimer as an efficient platform for production of intermediate-sized BsAbs and TsAbs in mammalian expression systems is proposed.
Improving the CH1-CK heterodimerization and pharmacokinetics of 4Dm2m, a novel potent CD4-antibody fusion protein against HIV-1
TLDR
A combination of three approaches have successfully increased the persistence of 4Dm2m in mice and is the first report on stabilized CH1-CK, which is potentially useful as a new heterodimerization scaffold for generation of bispecific and multispecific proteins with a more favorable pharmacokinetic profile.
Development of a bispecific antibody tetramerized through hetero‐associating peptides
TLDR
A novel method for constructing a highly functional antibody based on the hetero‐association of L27 domains that showed cytotoxic activity against EGFR‐expressing tumor cells by using CD16‐positive lymphocytes as effectors, and its cytotoxicity was comparable to that of a commercial therapeutic antibody.
Effect of domain order on the activity of bacterially produced bispecific single-chain Fv antibodies.
TLDR
It is demonstrated that the mechanism of inactivation of CD19xCD3 diabody under physiological conditions is initiated by a dissociation of the weaker (anti-CD3) VH/VL interface followed by domain swapping with the formation of non-active homodimers.
Fab-scFv fusion protein: an efficient approach to production of bispecific antibody fragments.
TLDR
An efficient approach for the production of a novel bispecific antibody fragment by genetically fusing a single-chain Fv to the C-terminus of either the light chain or the heavy chain of a Fab fragment of different antigen-binding specificity is described.
A new model for intermediate molecular weight recombinant bispecific and trispecific antibodies by efficient heterodimerization of single chain variable domains through fusion to a Fab-chain.
TLDR
It was found that the isolated CL:CH1 domain interaction was inefficient for secretion of heterodimers, however, when the complete Fab chains were used, secretion of a heterodimerized bispecific antibody was successful.
Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics.
TLDR
In vivo experiments indicated a higher stability and longer blood retention of tandem diabodies compared to single chain Fv fragments and diabody, properties that are particularly important for potential clinical applications.
Helix-stabilized Fv (hsFv) antibody fragments: substituting the constant domains of a Fab fragment for a heterodimeric coiled-coil domain.
TLDR
The format of a helix-stabilized Fv (hsFv) fragment can be a useful alternative to existing recombinant antibody formats, especially in cases where poor expression of Fab fragments or multimerization of scFv fragments is a problem.
An efficient route to the production of an IgG-like bispecific antibody.
TLDR
An efficient method is developed by using the natural dimerization mechanism between IgG heavy and light chains to produce a homogeneous bispecific IgG-like antibody product with each molecule containing four antigen binding sites, two for each of its target antigens.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 42 REFERENCES
Design and production of novel tetravalent bispecific antibodies
TLDR
Novel bispecific antibodies are produced by fusing the DNA encoding a single chain antibody after the C terminus (CH3-ScFv) or after the hinge (Hinge-Scfv) with an antibody of a different specificity.
Minibody: A novel engineered anti-carcinoembryonic antigen antibody fragment (single-chain Fv-CH3) which exhibits rapid, high-level targeting of xenografts.
TLDR
Purified minibodies retained high affinity for CEA (KA, 2 x 10(9) M(-1)) and demonstrated bivalent binding to antigen and tumor targeting properties were evaluated in vivo using athymic mice bearing LS174T human colon carcinoma xenografts.
A comparison of strategies to stabilize immunoglobulin Fv-fragments.
Fv-Fragments of antibodies may dissociate at low protein concentrations and are too unstable for many applications at physiological temperatures. To stabilize Fv-fragments against dissociation, we…
Engineering linear F(ab')2 fragments for efficient production in Escherichia coli and enhanced antiproliferative activity.
TLDR
Linear and thioether-linked F(ab')2 have very similar pharmacokinetic properties in normal mice, and their serum permanence times are respectively 7- and 8-fold longer than the corresponding Fab fragment.
Miniantibodies: use of amphipathic helices to produce functional, flexibly linked dimeric FV fragments with high avidity in Escherichia coli.
TLDR
The covalent bundle helix construct shows binding characteristics nearly identical to those of the much larger whole mouse antibody, resulting in substantially more stable immunoglobulin-antigen complexes than in the case of monovalent fragments.
Improving in vivo folding and stability of a single-chain Fv antibody fragment by loop grafting.
TLDR
The complementary determining regions (CDRs) from the fluorescein-binding antibody 4-4-20, which yields almost no soluble protein in periplasmic expression in Escherichia coli, were transplanted to the framework of the humanized antibody 4D5 and showed both a dramatic improvement in soluble expression and improved thermodynamic stability.
"Diabodies": small bivalent and bispecific antibody fragments.
TLDR
The design of small antibody fragments with two antigen-binding sites, which comprise a heavy-chain variable domain connected to a light- Chain variable domain on the same polypeptide chain (VH-VL), are described.
New protein engineering approaches to multivalent and bispecific antibody fragments.
  • A. Plückthun, P. Pack
  • Chemistry, Medicine
    Immunotechnology : an international journal of immunological engineering
  • 1997
TLDR
Recent progress in engineering multivalency from recombinant antibody fragments by using miniantibodies (scFv fragments linked with hinges and oligomerization domains), spontaneous scFv dimers with short linkers (diabodies), or chemically crosslinked antibody fragments are summarized.
Construction, expression, and activity of a bivalent bispecific single-chain antibody.
TLDR
Construction of a model bivalent bispecific molecule provides a foundation for future assembly of similar molecules designed to identify parameters involved in enhanced binding of antibodies due to avidity and dual specificity.
Assembly of a functional immunoglobulin Fv fragment in Escherichia coli.
TLDR
An expression system was developed that allows the production of a completely functional antigen-binding fragment of an antibody in Escherichia coli, and experiments showed that the affinity constant of the Fv fragment is identical to that of the native antibody McPC603, that there is one binding site for phosphorylcholine in the FV fragment, and that there are no inactive protein in the preparation.
...
1
2
3
4
5
...