Evidence map›Paper›PMID 37029216›Full record

ArticleCommunications biology2023

A high throughput bispecific antibody discovery pipeline.

Aude I Segaliny, Jayapriya Jayaraman, Xiaoming Chen, Jonathan Chong, Ryan Luxon, Audrey Fung, Qiwei Fu, Xianzhi Jiang, Rodrigo Rivera, Xiaoya Ma and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

19 citing papers in PubMed, 27 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

16 authors at 3 institutions in 2 countries.

Aude I Segaliny *Amberstone Biosciences, Inc., Irvine, CA, 92618, USA.
Jayapriya Jayaraman *Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA.
Xiaoming Chen *Amberstone Biosciences, Inc., Irvine, CA, 92618, USA.
Jonathan Chong *Amberstone Biosciences, Inc., Irvine, CA, 92618, USA.
Ryan Luxon *Amberstone Biosciences, Inc., Irvine, CA, 92618, USA.
Audrey FungAmberstone Biosciences, Inc., Irvine, CA, 92618, USA.ORCID 0000-0001-5375-2853
Qiwei FuAmberstone Biosciences, Inc., Irvine, CA, 92618, USA.
Xianzhi JiangAmberstone Biosciences, Inc., Irvine, CA, 92618, USA.
Rodrigo RiveraAmberstone Biosciences, Inc., Irvine, CA, 92618, USA.
Xiaoya MaAmberstone Biosciences, Inc., Irvine, CA, 92618, USA.
Ci RenAmberstone Biosciences, Inc., Irvine, CA, 92618, USA.
Jan ZimakDepartment of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, 92697, USA.
Per Niklas HeddeDepartment of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA.ORCID 0000-0002-2994-369X
Yonglei ShangAmberstone Biosciences, Inc., Irvine, CA, 92618, USA.
George WuAmberstone Biosciences, Inc., Irvine, CA, 92618, USA. george@amberstonebio.com.ORCID 0000-0001-8546-3220
Weian ZhaoDepartment of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA. weianz@uci.edu.ORCID 0000-0002-7794-9914
Aptose Biosciences (United States) · USUniversity of California, Irvine · USAmberstone Hospital · GB

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
NCI NIH HHS P30 CA062203
6 · The paper itself

Abstract

Bispecific antibodies (BsAbs) represent an emerging class of immunotherapy, but inefficiency in the current discovery has limited their broad clinical availability. Here we report a high throughput, agnostic, single-cell-based functional screening pipeline, comprising molecular and cell engineering for efficient generation of BsAb library cells, followed by functional interrogation at the single-cell level to identify and sort positive clones and downstream sequence identification and functionality characterization. Using a CD19xCD3 bispecific T cell engager (BiTE) as a model, we demonstrate that our single-cell platform possesses a high throughput screening efficiency of up to one and a half million variant library cells per run and can isolate rare functional clones at a low abundance of 0.008%. Using a complex CD19xCD3 BiTE-expressing cell library with approximately 22,300 unique variants comprising combinatorially varied scFvs, connecting linkers and VL/VH orientations, we have identified 98 unique clones, including extremely rare ones (~ 0.001% abundance). We also discovered BiTEs that exhibit novel properties and insights to design variable preferences for functionality. We expect our single-cell platform to not only increase the discovery efficiency of new immunotherapeutics, but also enable identifying generalizable design principles based on an in-depth understanding of the inter-relationships between sequence, structure, and function.

Indexed as

Antibodies, BispecificHigh-Throughput Screening AssaysT-LymphocytesImmunotherapySingle-Cell AnalysisAntibodies, Bispecific

Identifiers

PMID37029216
PMCPMC10082157
OpenAlexW4362696694

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.