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

  title={The first constant domain (CH1 and CL) of an antibody used as heterodimerization domain for bispecific miniantibodies},
  author={Kristian M. M{\"u}ller and Katja M. Arndt and Wolfgang Strittmatter and Andreas Pl{\"u}ckthun},
  journal={FEBS Letters},

Fab Chains As an Efficient Heterodimerization Scaffold for the Production of Recombinant Bispecific and Trispecific Antibody Derivatives1

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

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

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.

Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics.

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.

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.

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.



Design and production of novel tetravalent bispecific antibodies

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.

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.

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.

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.

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.

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. PlückthunP. Pack
  • Biology, Chemistry
    Immunotechnology : an international journal of immunological engineering
  • 1997

Assembly of a functional immunoglobulin Fv fragment in Escherichia coli.

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.