Evidence map›Paper›PMID 40081946›Full record

ArticleJournal for immunotherapy of cancer2025

Potent and durable control of mesothelin-expressing tumors by a novel T cell-secreted bi-specific engager.

Paris Kosti, Johan Abram-Saliba, Laetitia Pericou-Troquier, Sarah Pavelot, Tiphaine Ruggeri, Marc Laffaille, Melita Irving, George Coukos, Evripidis Lanitis, Steven M Dunn

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

10 authors.

Paris KostiDepartment of Oncology, Ludwig Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland.
Johan Abram-SalibaDepartment of Oncology, Ludwig Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland.
Laetitia Pericou-TroquierDepartment of Oncology, Ludwig Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland.
Sarah PavelotDepartment of Oncology, Ludwig Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland.
Tiphaine RuggeriDepartment of Oncology, Ludwig Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland.
Marc LaffailleDepartment of Oncology, Ludwig Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland.
Melita IrvingDepartment of Oncology, Ludwig Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-6849-7194
George CoukosDepartment of Oncology, Ludwig Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland.
Evripidis Lanitis *Department of Oncology, Ludwig Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-8194-5414
Steven M Dunn *Department of Oncology, Ludwig Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland steven.dunn@chuv.ch.ORCID http://orcid.org/0000-0002-7402-9581

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe glycosylphosphatidylinositol-anchored cell surface protein mesothelin (MSLN) shows elevated expression in many malignancies and is an established clinical-stage target for antibody-directed therapeutic strategies. Of these, the harnessing of autologous patient T cells via engineered anti-MSLN chimeric antigen receptors (CAR-T) is an approach garnering considerable interest. Although generally shown to target tumor MSLN safely, CAR-T trials have failed to deliver the impressive curative or response metrics achieved for hematological malignancies using the same technology. A need exists, therefore, for improved anti-MSLN molecules and/or more optimal ways to leverage immune effector cells.

methodsWe performed ELISA, label-free kinetic binding assays, FACS, Western blotting, and transient recombinant MSLN expression to characterize the recognition properties of a novel CAR-active human scFv clone, LABC-13F08. To investigate T cell redirection, we conducted kinetic IncuCyte co-culture killing assays using transduced primary T cells and MSLN

resultsThe LABC-13F08 scFv is highly unusual and distinct from existing (pre)clinical anti-MSLN antibody fragments, exhibiting an absolute requirement for divalent cations to drive MSLN recognition. As a monovalent BiTE, LABC-13F08 demonstrates robust in vitro potency. Additionally, primary human T cells engineered for constitutive secretion of the 13F08 BiTE exhibit strong antitumor activity toward in vivo ovarian and mesothelioma xenograft models and show encouraging levels of monotherapy control in a challenging pancreatic model. LABC-13F08 BiTE secreted from engineered T cells (BiTE-T) can both recruit non-engineered bystander T cells and also induce activation-dependent MSLN-independent bystander killing of cells lacking cognate antigen. To address safety concerns, 13F08 BiTE-T cells can be rapidly targeted for clearance via a molecular "off" switch.

conclusionsThe novel LABC-13F08 scFv exhibits a mode of binding to MSLN which is not observed in typical anti-MSLN antibodies. Efficacious targeting by a T cell secreted engager would represent a clinically differentiated approach for the treatment of MSLN

Indexed as

GPI-Linked ProteinsImmunotherapy, AdoptiveReceptors, Chimeric AntigenT-LymphocytesAnimalsCell Line, TumorFemaleHumansMesothelinMiceXenograft Model Antitumor AssaysGPI-Linked ProteinsMesothelinMSLN protein, humanMsln protein, mouseReceptors, Chimeric AntigenAdoptive cell therapy - ACTBispecific T cell engager - BiTEImmunotherapySolid tumorT cell

Identifiers

PMID40081946
PMCPMC11907088

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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.