Evidence map›Paper›PMID 34257348›Full record

ArticleScientific reports2021

Generation of T-cell-redirecting bispecific antibodies with differentiated profiles of cytokine release and biodistribution by CD3 affinity tuning.

Lauric Haber, Kara Olson, Marcus P Kelly, Alison Crawford, David J DiLillo, Richard Tavaré, Erica Ullman, Shu Mao, Lauren Canova, Olga Sineshchekova and 34 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
9.3field-weighted citation impact, top 1% 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

87 citing papers in PubMed, 98 citations in OpenAlex.

  1. Article
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  7. T cell engagers in autoimmune diseases.Nature reviews. Immunology · 2026
    Review
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27 more citing papers are in PubMed but not listed here.

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

44 authors at 3 institutions in 2 countries.

Lauric HaberRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA. Lauric.haber@regeneron.com.
Kara OlsonRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Marcus P KellyRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Alison CrawfordRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
David J DiLilloRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Richard TavaréRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Erica UllmanRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Shu MaoRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Lauren CanovaRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Olga SineshchekovaRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Jennifer FinneyRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Arpita PawasheRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Supriya PatelRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Ryan McKayRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Sahar RizviRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Ermelinda DamkoRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Danica ChiuAstraZeneca, Cambridge, UK.
Kristin VazzanaRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Priyanka RamRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Katja MohrsRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Amanda D'OrvilliersRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Jenny XiaoRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Sosina MakonnenRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Carlos HickeyRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Cody ArnoldRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Jason GiurleoRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Ya Ping ChenRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Courtney ThwaitesLonza, Slough, UK.
Drew DudgeonRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Kevin BrayRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Ashique RafiqueRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Tammy HuangRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Frank DelfinoRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Aynur HermannRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Jessica R KirshnerRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Marc W RetterRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Robert BabbRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Douglas MacDonaldRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Gang ChenRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
William C OlsonRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Gavin ThurstonRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Samuel DavisRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
John C LinRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Eric SmithRegeneron Pharmaceuticals, Inc, Tarrytown, NY, 10591, USA.
Regeneron (United States) · USAstraZeneca (United Kingdom) · GBLonza (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

T-cell-redirecting bispecific antibodies have emerged as a new class of therapeutic agents designed to simultaneously bind to T cells via CD3 and to tumor cells via tumor-cell-specific antigens (TSA), inducing T-cell-mediated killing of tumor cells. The promising preclinical and clinical efficacy of TSAxCD3 antibodies is often accompanied by toxicities such as cytokine release syndrome due to T-cell activation. How the efficacy and toxicity profile of the TSAxCD3 bispecific antibodies depends on the binding affinity to CD3 remains unclear. Here, we evaluate bispecific antibodies that were engineered to have a range of CD3 affinities, while retaining the same binding affinity for the selected tumor antigen. These agents were tested for their ability to kill tumor cells in vitro, and their biodistribution, serum half-life, and anti-tumor activity in vivo. Remarkably, by altering the binding affinity for CD3 alone, we can generate bispecific antibodies that maintain potent killing of TSA + tumor cells but display differential patterns of cytokine release, pharmacokinetics, and biodistribution. Therefore, tuning CD3 affinity is a promising method to improve the therapeutic index of T-cell-engaging bispecific antibodies.

Indexed as

Antibodies, BispecificCD3 ComplexCytokinesT-LymphocytesAnimalsAntibody AffinityAntigens, NeoplasmCell Line, TumorHumansLymphocyte ActivationMiceTissue DistributionXenograft Model Antitumor AssaysAntibodies, BispecificAntigens, NeoplasmCD3 ComplexCytokines

Identifiers

PMID34257348
PMCPMC8277787
OpenAlexW3181390667

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LicenceCC BY
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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.