Evidence map›Paper›PMID 28827777›Full record

ArticleScientific reports2017

Efficient generation of bispecific IgG antibodies by split intein mediated protein trans-splicing system.

Lei Han, Junsheng Chen, Kai Ding, Huifang Zong, Yueqing Xie, Hua Jiang, Baohong Zhang, Huili Lu, Weihan Yin, John Gilly and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

40 citing papers in PubMed, 69 citations in OpenAlex.

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  16. Article
  17. Construction of IgG-FabScientific reports · 2023
    Article
  18. Article
  19. Article
  20. Universal chimeric FcActa pharmaceutica Sinica. B · 2023
    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

11 authors at 2 institutions in 2 countries.

Lei HanEngineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Junsheng ChenEngineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Kai DingEngineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Huifang ZongEngineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Yueqing XieJecho Laboratories, Inc, Frederick, MD, USA.
Hua JiangJecho Laboratories, Inc, Frederick, MD, USA.
Baohong ZhangEngineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Huili LuEngineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.ORCID 0000-0002-8748-7899
Weihan YinSchool of Life Science, East China Normal University, Shanghai, China.
John GillyJecho Biopharmaceuticals Co., Ltd, Tianjin, China.
Jianwei ZhuEngineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China. jianweiz@sjtu.edu.cn.
Shanghai Jiao Tong University · CNEast China Normal University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many methods have been developed to produce bispecific antibodies (BsAbs) for industrial application. However, huge challenges still remain in synthesizing whole length BsAbs, including their assembly, stability, immunogenicity, and pharmacodynamics. Here we present for first time a generic technology platform of generating bispecific IgG antibodies, "Bispecific Antibody by Protein Trans-splicing (BAPTS)". Different from published methods, we assembled two parental antibody fragments in the hinge region by the protein trans-splicing reaction of a split intein to generate BsAbs without heavy/heavy and light/heavy chain mispairing. Utilizing this simple and efficient approach, there have been several BsAbs (CD3×HER2, CD3×EGFR, EGFR×HER2) synthesized to demonstrate its broad applicability. Correctly paired mAb arms were assembled to form BsAbs that were purified through protein A affinity chromatography to demonstrate industrial applicability at large scale. Further, the products were characterized through physical-biochemistry properties and biological activities to confirm expected quality of the products from "BAPTS". More importantly, correct pairing was confirmed by mass spectrum. Proof-of-concept studies with CD3×HER2 BsAb (T-cell recruitment) demonstrated superior bioactivity compared with trastuzumab. The results of undetectable mispairing and high biological activity have indicated that this method has the potential to be utilized to manufacture BsAbs with high efficiency at industrial scale.

Indexed as

Protein SplicingTrans-SplicingAnimalsAntibodies, BispecificCD3 ComplexCell ProliferationErb-b2 Receptor Tyrosine KinasesErbB ReceptorsFemaleHumansImmunoglobulin GMiceMice, Inbred NODMice, SCIDProtein EngineeringStomach NeoplasmsAntibodies, BispecificCD3 ComplexEGFR protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesErbB ReceptorsImmunoglobulin G

Identifiers

PMID28827777
PMCPMC5567192
OpenAlexW2744157341

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.