Evidence map›Paper›PMID 34768776›Full record

ArticleInternational journal of molecular sciences2021

Simultaneous Inhibition of PD-1 and Stimulation of CD40 Signaling Pathways by Anti-PD-L1/CD40L Bispecific Fusion Protein Synergistically Activate Target and Effector Cells.

Madhu S Pandey, Chunlei Wang, Scott Umlauf, Shihua Lin

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 28% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

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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

4 authors at 1 institution in 1 country.

Madhu S PandeyBioassay Development, Analytical Sciences, Biopharmaceutical Development, R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Chunlei WangPhysicochemical-Analytical Sciences, Biopharmaceutical Development, AstraZeneca, R&D, Gaithersburg, MD 20878, USA.
Scott UmlaufBioassay Development, Analytical Sciences, Biopharmaceutical Development, R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Shihua LinBioassay Development, Analytical Sciences, Biopharmaceutical Development, R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
AstraZeneca (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bispecific antibodies (BsAbs) or fusion proteins (BsAbFPs) present a promising strategy for cancer immunotherapy. Numerous BsAbs targeting coinhibitory and costimulatory pathways have been developed for retargeting T cells and antigen presenting cells (APCs). It is challenging to assess the potency of BsAb that engages two different signaling pathways simultaneously in a single assay format, especially when the two antigen targets are expressed on different cells. To explore the potency of anti-PD-L1/CD40L BsAbFP, a fusion protein that binds to human CD40 and PD-L1, we engineered CHO cells as surrogate APCs that express T cell receptor activator and PD-L1, Jurkat cells with PD-1 and NFAT-luciferase reporter as effector T cells, and Raji cell with NFkB-luciferase that endogenously expresses CD40 as accessory B cells. A novel reporter gene bioassay was developed using these cell lines that allows anti-PD-L1/CD40L BsAbFP to engages both PD-1/PD-L1 and CD40/CD40L signaling pathways in one assay. As both reporters use firefly luciferase, the effects of activating both signaling pathways is observed as an increase in luminescence, either as a higher upper asymptote, a lower EC

Indexed as

AnimalsAntibodies, BispecificAntibodies, MonoclonalAntigen-Presenting CellsAntigensB7-H1 AntigenCD40 AntigensCD40 LigandCHO CellsCricetulusHumansJurkat CellsProgrammed Cell Death 1 ReceptorSignal TransductionAntibodies, BispecificAntibodies, MonoclonalAntigensB7-H1 AntigenCD274 protein, humanCD40 AntigensCD40 LigandPDCD1 protein, humanProgrammed Cell Death 1 Receptorbioassaybispecific antibodymechanism of actionpotencyqualification

Identifiers

PMID34768776
PMCPMC8583728
OpenAlexW3211325563

What OpenQuestion holds

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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.