Evidence map›Paper›PMID 37230538›Full record

ArticleJournal for immunotherapy of cancer2023

Anti-HVEM mAb therapy improves antitumoral immunity both in vitro and in vivo, in a novel transgenic mouse model expressing human HVEM and BTLA molecules challenged with HVEM expressing tumors.

Clémence Demerlé, Laurent Gorvel, Marielle Mello, Sonia Pastor, Clara Degos, Ana Zarubica, Fabien Angelis, Frédéric Fiore, Jacques A Nunes, Bernard Malissen and 5 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

12 citing papers in PubMed, 17 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. A novel HVEM-Fc recombinant protein for lung cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2025
    Article
  5. Article
  6. The Evolving Applications of Bispecific Antibodies: Reaping the Harvest of Early Sowing and Planting New Seeds.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Clémence Demerlé *Department of Immunomonitoring, Institut Paoli-Calmettes, Marseille, France.
Laurent Gorvel *Department of Immunomonitoring, Institut Paoli-Calmettes, Marseille, France.ORCID 0000-0001-7526-261X
Marielle Mello *Centre d'Immunophénomique-CIPHE (PHENOMIN), Marseille, France.
Sonia PastorTeam Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille, Marseille, France.
Clara DegosDepartment of Immunomonitoring, Institut Paoli-Calmettes, Marseille, France.
Ana ZarubicaCentre d'Immunophénomique-CIPHE (PHENOMIN), Marseille, France.
Fabien AngelisCentre d'Immunophénomique-CIPHE (PHENOMIN), Marseille, France.
Frédéric FioreCentre d'Immunophénomique-CIPHE (PHENOMIN), Marseille, France.ORCID 0000-0001-7955-6594
Jacques A NunesTeam Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille, Marseille, France.ORCID 0000-0003-4865-0400
Bernard MalissenCentre d'Immunophénomique-CIPHE (PHENOMIN), Marseille, France.
Laurent GreillierAix-Marseille University, Marseille, France.
Geoffrey GuittardTeam Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille, Marseille, France geoffrey.guittard@inserm.fr.ORCID 0000-0002-6061-8553
Hervé LucheCentre d'Immunophénomique-CIPHE (PHENOMIN), Marseille, France.
Fabrice BarlesiDepartment of Multidisciplinary Oncology and Therapeutic Innovations, CHU NORD, Marseille, France.
Daniel OliveDepartment of Immunomonitoring, Institut Paoli-Calmettes, Marseille, France.ORCID 0000-0003-1299-4113
Immunité et Cancer · FRCentre d’Immunologie de Marseille-Luminy · FRAix-Marseille Université · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTumor necrosis factor superfamily member 14 (TNFRSF14)/herpes virus entry mediator (HVEM) is the ligand for B and T lymphocyte attenuator (BTLA) and CD160-negative immune co-signaling molecules as well as viral proteins. Its expression is dysregulated with an overexpression in tumors and a connection with tumors of adverse prognosis.

methodsWe developed C57BL/6 mouse models co-expressing human (hu)BTLA and huHVEM as well as antagonistic monoclonal antibodies (mAbs) that completely prevent the interactions of HVEM with its ligands.

resultsHere, we show that the anti-HVEM18-10 mAb increases primary human αβ-T cells activity alone (CIS-activity) or in the presence of HVEM-expressing lung or colorectal cancer cells in vitro (TRANS-activity). Anti-HVEM18-10 synergizes with antiprogrammed death-ligand 1 (anti-PD-L1) mAb to activate T cells in the presence of PD-L1-positive tumors, but is sufficient to trigger T cell activation in the presence of PD-L1-negative cells. In order to better understand HVEM18-10 effects in vivo and especially disentangle its CIS and TRANS effects, we developed a knockin (KI) mouse model expressing human BTLA (huBTLA

conclusionsAltogether, our preclinical models validate anti-HVEM18-10 as a promising therapeutic antibody to use in clinics as a monotherapy or in combination with existing immunotherapies (antiprogrammed cell death protein 1/anti-PD-L1/anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4)).

Indexed as

CD8-Positive T-LymphocytesNeoplasmsReceptors, Tumor Necrosis Factor, Member 14AnimalsAntibodies, MonoclonalHumansMiceMice, Inbred C57BLMice, TransgenicReceptors, ImmunologicAntibodies, MonoclonalBTLA protein, humanReceptors, ImmunologicReceptors, Tumor Necrosis Factor, Member 14costimulatory and inhibitory T-cell receptorsimmunotherapylymphocyte activationlymphocytes, tumor-infiltratingT-lymphocytes

Identifiers

PMID37230538
PMCPMC10231015
OpenAlexW4378211516

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

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.