Evidence map›Paper›PMID 42285608›Full record

ArticleJournal for immunotherapy of cancer2026

Blinatumomab bypasses CD28 blockade to sustain T-cell cytotoxicity and improve survival in a xenograft B-ALL model.

Geovana S F Leite, John Sullivan, Dimitrios Filioglou, Matina Kounelis, Helena Batatinha, Richard J Simpson, Emmanuel Katsanis

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Geovana S F LeiteDepartment of Pediatrics, The University of Arizona College of Medicine Tucson, Tucson, Arizona, USA.ORCID http://orcid.org/0000-0002-4692-890X
John SullivanSchool of Nutritional Sciences and Wellness, University of Arizona, Tucson, Arizona, USA.
Dimitrios FilioglouDepartment of Pediatrics, The University of Arizona College of Medicine Tucson, Tucson, Arizona, USA.ORCID http://orcid.org/0000-0002-5469-6889
Matina KounelisDepartment of Pediatrics, The University of Arizona College of Medicine Tucson, Tucson, Arizona, USA.
Helena BatatinhaSchool of Nutritional Sciences and Wellness, University of Arizona, Tucson, Arizona, USA.
Richard J SimpsonDepartment of Pediatrics, The University of Arizona College of Medicine Tucson, Tucson, Arizona, USA.ORCID http://orcid.org/0000-0002-7064-6881
Emmanuel KatsanisDepartment of Pediatrics, The University of Arizona College of Medicine Tucson, Tucson, Arizona, USA ekatsani@arizona.edu.ORCID http://orcid.org/0000-0003-1466-6965

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRelapse and graft-versus-host disease (GvHD) remain primary causes of treatment failure in patients with B-cell acute lymphoblastic leukemia (B-ALL) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). While abatacept (ABATA) effectively mitigates GvHD via CD28-costimulation blockade, there is significant concern that it concurrently diminishes graft-versus-leukemia (GvL) effects, potentially leading to higher relapse rates. We investigated whether blinatumomab (BLINA) retains antileukemic efficacy in the presence of ABATA using in vitro assays and humanized NOD.Cg-Prkdc

methodsIn vitro and ex vivo flow cytometry-based cytotoxicity, degranulation (CD107a), cytokine production (interferon (IFN)-γ), and activation-marker (CD25, CD69, CD137, OX40) assays were performed using healthy donor peripheral blood mononuclear cells (PBMCs) (pretreated±ABATA) against leukemia or lymphoma cell lines (RS4;11, NALM-6, and JEKO-1) in the presence or not of BLINA. In vivo human PBMC-reconstituted NSG-IL-15 mice bearing RS4;11 B-ALL xenografts were treated with vehicle, monotherapy (BLINA or ABATA), or combination therapy. Leukemia burden and immune reconstitution were assessed through week 4; GvHD scores and overall survival were monitored longitudinally.

resultsABATA did not impair BLINA-mediated cytotoxicity across multiple effector-to-target ratios against any of the cell lines, nor did it reduce BLINA-induced degranulation, IFN-γ production, or activation marker expression. In vivo, BLINA monotherapy significantly reduced leukemia burden, but resulted in early mortality due to severe GvHD. Conversely, ABATA markedly reduced GvHD severity. The combination of BLINA and ABATA preserved potent antileukemic efficacy while significantly extending median survival by 35 days compared with tumor controls (p<0.0001). Although ABATA attenuated T-cell expansion and differentiation, BLINA-driven cytotoxic function was maintained, even after prolonged in vivo exposure to cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA-4-Ig).

conclusionThese findings provide preclinical proof-of-concept that BLINA and ABATA can be combined to uncouple GvL from GvHD. This strategy preserves CD28-independent T-cell cytotoxicity while limiting allo-reactivity, providing a strong rationale for investigating this combination in the post-transplant setting.

Indexed as

Antibodies, BispecificCD28 AntigensAnimalsDisease Models, AnimalFemaleGraft vs Host DiseaseHumansMiceMice, Inbred NODXenograft Model Antitumor AssaysAntibodies, BispecificblinatumomabCD28 AntigensBispecific T cell engager - BiTEGraft versus host disease - GVHDGraft versus leukemiaImmunotherapyLeukemia

Identifiers

PMID42285608
PMCPMC13289407

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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.