Evidence map›Paper›PMID 35134130›Full record

ArticleBlood2022

Unbiased cell surface proteomics identifies SEMA4A as an effective immunotherapy target for myeloma.

Georgina S F Anderson, Jose Ballester-Beltran, George Giotopoulos, Jose A Guerrero, Sylvanie Surget, James C Williamson, Tsz So, David Bloxham, Anna Aubareda, Ryan Asby and 18 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.6field-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

26 citing papers in PubMed, 37 citations in OpenAlex.

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  13. Are we there yet? CAR-T therapy in multiple myeloma.British journal of haematology · 2024
    Review
  14. Review
  15. Mapping the cancer surface proteome in search of target antigens for immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 8 institutions in 2 countries.

Georgina S F AndersonMRC Toxicology Unit and.ORCID 0000-0003-4747-1689
Jose Ballester-BeltranDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-3287-2925
George GiotopoulosDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0003-1390-6592
Jose A GuerreroMRC Toxicology Unit and.
Sylvanie SurgetDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom.
James C WilliamsonDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
Tsz SoMRC Toxicology Unit and.
David BloxhamCambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
Anna AubaredaMRC Toxicology Unit and.
Ryan AsbyDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0001-5077-3798
Ieuan WalkerMRC Toxicology Unit and.
Lesley JenkinsonCRUK-AstraZeneca Antibody Alliance Laboratory, Cambridge, United Kingdom.
Elizabeth J SoilleuxDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
James P RoyMRC Toxicology Unit and.ORCID 0000-0001-9178-8953
Ana TeodósioMRC Toxicology Unit and.ORCID 0000-0002-1386-6730
Catherine FickenMRC Toxicology Unit and.ORCID 0000-0003-4764-210X
Leah Officer-JonesMRC Toxicology Unit and.ORCID 0000-0002-3690-2386
Sara NasserTranslational Genomics Research Institute, Phoenix, AZ.
Sheri SkergetTranslational Genomics Research Institute, Phoenix, AZ.ORCID 0000-0001-5153-0835
Jonathan J KeatsTranslational Genomics Research Institute, Phoenix, AZ.ORCID 0000-0003-4375-7399
Peter GreavesGenetics and Genome Biology, University of Leicester, Leicester, United Kingdom.
Yu-Tzu TaiDana Farber Cancer Institute, Boston, MA; and.
Kenneth C AndersonDana Farber Cancer Institute, Boston, MA; and.
Marion MacFarlaneMRC Toxicology Unit and.ORCID 0000-0001-7886-1159
James E ThaventhiranMRC Toxicology Unit and.ORCID 0000-0001-8616-074X
Brian J P HuntlyDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0003-0312-161X
Paul J LehnerCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.
Michael A ChapmanMRC Toxicology Unit and.ORCID 0000-0001-8342-0606
MRC Toxicology Unit · GBUniversity of Cambridge · GBTranslational Genomics Research Institute · USWellcome/MRC Cambridge Stem Cell Institute · GBCambridge University Hospitals NHS Foundation Trust · GBDana-Farber Cancer Institute · USAstraZeneca (United Kingdom) · GBUniversity of Leicester · GB

Funding

Cancer Research UK 24724Cancer Research UK 25508Medical Research Council MC_UU_00025/10Medical Research Council MC_UU_00025/4Wellcome Trust 210688/Z/18/Z
6 · The paper itself

Abstract

The accessibility of cell surface proteins makes them tractable for targeting by cancer immunotherapy, but identifying suitable targets remains challenging. Here we describe plasma membrane profiling of primary human myeloma cells to identify an unprecedented number of cell surface proteins of a primary cancer. We used a novel approach to prioritize immunotherapy targets and identified a cell surface protein not previously implicated in myeloma, semaphorin-4A (SEMA4A). Using knock-down by short-hairpin RNA and CRISPR/nuclease-dead Cas9 (dCas9), we show that expression of SEMA4A is essential for normal myeloma cell growth in vitro, indicating that myeloma cells cannot downregulate the protein to avoid detection. We further show that SEMA4A would not be identified as a myeloma therapeutic target by standard CRISPR/Cas9 knockout screens because of exon skipping. Finally, we potently and selectively targeted SEMA4A with a novel antibody-drug conjugate in vitro and in vivo.

Indexed as

Multiple MyelomaSemaphorinsCell MembraneHumansImmunologic FactorsImmunotherapyMembrane ProteinsProteomicsImmunologic FactorsMembrane ProteinsSEMA4A protein, humanSemaphorins

Identifiers

PMID35134130
PMCPMC11022854
OpenAlexW4211099837

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.