Evidence map›Paper›PMID 26593903›Full record

ArticleInternational journal of molecular sciences2015

TriFabs--Trivalent IgG-Shaped Bispecific Antibody Derivatives: Design, Generation, Characterization and Application for Targeted Payload Delivery.

Klaus Mayer, Anna-Lena Baumann, Michael Grote, Stefan Seeber, Hubert Kettenberger, Sebastian Breuer, Tobias Killian, Wolfgang Schäfer, Ulrich Brinkmann

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Klaus MayerRoche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, D82377 Penzberg, Germany. klaus.mayer.km1@roche.com.
Anna-Lena BaumannRoche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, D82377 Penzberg, Germany. annalenabaumann@web.de.
Michael GroteRoche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, D82377 Penzberg, Germany. michael.grote@roche.com.
Stefan SeeberRoche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, D82377 Penzberg, Germany. stefan.seeber@roche.com.
Hubert KettenbergerRoche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, D82377 Penzberg, Germany. hubert.kettenberger@roche.com.
Sebastian BreuerRoche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, D82377 Penzberg, Germany. sebastian.breuer@roche.com.
Tobias KillianRoche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, D82377 Penzberg, Germany. tobias.killian@roche.com.
Wolfgang SchäferRoche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, D82377 Penzberg, Germany. wolfgangschaefer@onlinehome.de.
Ulrich BrinkmannRoche Pharma Research & Early Development, Large Molecule Research, Roche Innovation Center Penzberg, D82377 Penzberg, Germany. ulrich.brinkmann@roche.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TriFabs are IgG-shaped bispecific antibodies (bsAbs) composed of two regular Fab arms fused via flexible linker peptides to one asymmetric third Fab-sized binding module. This third module replaces the IgG Fc region and is composed of the variable region of the heavy chain (VH) fused to CH3 with "knob"-mutations, and the variable region of the light chain (VL) fused to CH3 with matching "holes". The hinge region does not contain disulfides to facilitate antigen access to the third binding site. To compensate for the loss of hinge-disulfides between heavy chains, CH3 knob-hole heterodimers are linked by S354C-Y349C disulphides, and VH and VL of the stem region may be linked via VH44C-VL100C disulphides. TriFabs which bind one antigen bivalent in the same manner as IgGs and the second antigen monovalent "in between" these Fabs can be applied to simultaneously engage two antigens, or for targeted delivery of small and large (fluorescent or cytotoxic) payloads.

Indexed as

Antibodies, BispecificImmunoglobulin Fab FragmentsImmunoglobulin GAntibody AffinityBinding SitesDisulfidesDrug CarriersDrug Delivery SystemsEpitopesGenetic EngineeringHumansImmunoconjugatesProtein BindingProtein MultimerizationProtein StabilityTemperatureAntibodies, BispecificDisulfidesDrug CarriersEpitopesImmunoconjugatesImmunoglobulin Fab FragmentsImmunoglobulin GCD33disulfide stabilizationGPC3imagingknob-into-holeLeYpayload deliverysaporin

Identifiers

PMID26593903
PMCPMC4661895

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.