Evidence map›Paper›PMID 21777442›Full record

ArticleBMC biotechnology2011

Site-specific modification of ED-B-targeting antibody using intein-fusion technology.

Sina Möhlmann, Peter Bringmann, Simone Greven, Axel Harrenga

Open access · goldAbstract read
In one paragraph

Article in BMC biotechnology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.4field-weighted citation impact, top 6% of its field
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

20 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. A mesophilic cysteine-less split intein for proteinProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  9. Improved protein splicing using embedded split inteins.Protein science : a publication of the Protein Society · 2018
    Article
  10. Review
  11. Article
  12. Review
  13. Design of a Split Intein with Exceptional Protein Splicing Activity.Journal of the American Chemical Society · 2016
    Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Streamlined expressed protein ligation using split inteins.Journal of the American Chemical Society · 2013
    Article
  20. Article
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

4 authors at 2 institutions in 2 countries.

Sina MöhlmannBayer Healthcare Research Center, Aprather Weg 18a, 42113 Wuppertal, Germany.
Peter Bringmann
Simone Greven
Axel Harrenga
Bayer (United States) · USBayer (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA promising new approach in cancer therapy is the use of tumor specific antibodies coupled to cytotoxic agents. Currently these immunoconjugates are prepared by rather unspecific coupling chemistries, resulting in heterogeneous products. As the drug load is a key parameter for the antitumor activity, site-specific strategies are desired. Expressed protein ligation (EPL) and protein trans-splicing (PTS) are methods for the specific C-terminal modification of a target protein. Both include the expression as an intein fusion protein, followed by the exchange of the intein for a functionalized moiety.

resultsA full-length IgG specific for fibronectin ED-B was expressed as fusion protein with an intein (Mxe GyrA or Npu DnaE) attached to each heavy chain. In vitro protocols were established to site-specifically modify the antibodies in high yields by EPL or PTS, respectively. Although reducing conditions had to be employed during the process, the integrity or affinity of the antibody was not affected. The protocols were used to prepare immunoconjugates containing two biotin molecules per antibody, attached to the C-termini of the heavy chains.

conclusionFull-length antibodies can be efficiently and site-specifically modified at the C-termini of their heavy chains by intein-fusion technologies. The described protocols can be used to prepare immunoconjugates of high homogeneity and with a defined drug load of two. The attachment to the C-termini is expected to retain the affinity and effector functions of the antibodies.

Indexed as

Amino Acid SequenceElectrophoresis, Polyacrylamide GelFibronectinsHumansImmunoconjugatesImmunoglobulin GInteinsMolecular Sequence DataProtein EngineeringRecombinant Fusion ProteinsTrans-SplicingFibronectinsFN1 protein, humanImmunoconjugatesImmunoglobulin GRecombinant Fusion Proteins

Identifiers

PMID21777442
PMCPMC3154154
OpenAlexW2094385207

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.