Evidence map›Paper›PMID 25970007›Full record

ArticlemAbs2015

Enhancement of antibody-dependent cell-mediated cytotoxicity by endowing IgG with FcαRI (CD89) binding.

M Jack Borrok, Nadia M Luheshi, Nurten Beyaz, Gareth C Davies, James W Legg, Herren Wu, William F Dall'Acqua, Ping Tsui

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
4.3field-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

45 citing papers in PubMed, 67 citations in OpenAlex.

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  11. New immune cell engagers for cancer immunotherapy.Nature reviews. Immunology · 2024
    Review
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  19. The present and future of immunocytokines for cancer treatment.Cellular and molecular life sciences : CMLS · 2022
    Review
  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

8 authors at 2 institutions in 2 countries.

M Jack Borroka Antibody Discovery and Protein Engineering; Medimmune Ltd. ; Gaithersburg , MD , USA.
Nadia M Luheshi
Nurten Beyaz
Gareth C Davies
James W Legg
Herren Wu
William F Dall'Acqua
Ping Tsui
AstraZeneca (Germany) · DEAimmune Therapeutics (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fc effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP) are crucial to the efficacy of many antibody therapeutics. In addition to IgG, antibodies of the IgA isotype can also promote cell killing through engagement of myeloid lineage cells via interactions between the IgA-Fc and FcαRI (CD89). Herein, we describe a unique, tandem IgG1/IgA2 antibody format in the context of a trastuzumab variable domain that exhibits enhanced ADCC and ADCP capabilities. The IgG1/IgA2 tandem Fc format retains IgG1 FcγR binding as well as FcRn-mediated serum persistence, yet is augmented with myeloid cell-mediated effector functions via FcαRI/IgA Fc interactions. In this work, we demonstrate anti-human epidermal growth factor receptor-2 antibodies with the unique tandem IgG1/IgA2 Fc can better recruit and engage cytotoxic polymorphonuclear (PMN) cells than either the parental IgG1 or IgA2. Pharmacokinetics of IgG1/IgA2 in BALB/c mice are similar to the parental IgG, and far surpass the poor serum persistence of IgA2. The IgG1/IgA2 format is expressed at similar levels and with similar thermal stability to IgG1, and can be purified via standard protein A chromatography. The tandem IgG1/IgA2 format could potentially augment IgG-based immunotherapeutics with enhanced PMN-mediated cytotoxicity while avoiding many of the problems associated with developing IgAs.

Indexed as

Immunoglobulin GAnimalsAntibody-Dependent Cell CytotoxicityAntigens, CDErb-b2 Receptor Tyrosine KinasesFemaleHEK293 CellsHumansImmunoglobulin ALeukocytesMaleMiceMice, Inbred BALB CPhagocytosisReceptors, FcReceptors, IgGAntigens, CDERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesFc(alpha) receptorImmunoglobulin AImmunoglobulin GReceptors, FcReceptors, IgGADCCADCC, antibody-dependent cell-mediated cytotoxicityADCP, antibody-dependent cell-mediated phagocytosisAUC, area under the curve; CL, clearance rateCD89CDC, complement dependent cytotoxicityCmax, maximum serum concentrationDSC, differential scanning calorimetryE:T ratio, effector to target ratioFCM, flow cytometryFcRn, neonatal Fc receptorFcαRIFcγR, Fc gamma receptorHER2, human epithelial receptor twoIgAIgA, immunoglobulin AIgG, immunoglobulin GLDH, lactate dehydrogenasemacrophagemonoclonal antibodyMΦ, macrophageneutrophilNK, natural killerPBMC, peripheral blood mononuclear cellPK, pharmacokineticsPMN, polymorphonuclearSPR, surface plasmon resonanceT½, half-lifeTAA, tumor associated antigenstandemtrastuzumabVss, central compartment volume of distribution

Identifiers

PMID25970007
PMCPMC4623516
OpenAlexW1878923342

What OpenQuestion holds

Textmetadata
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.