Evidence map›Paper›PMID 42236119›Full record

ArticleJournal for immunotherapy of cancer2026

Systemic pre-conditioning favors effector over exhausted CD8 T-cell subsets following Sup2-IL33 armored CAR T-cell therapy.

Shannon L Ferry, Leena Abdullah, Akshaya Balasubramanian, Elizabeth C Nowak, Allison Carl, Alexandrea Turnquist, Asmaa Mohamed, Edward Usherwood, Mark Sundrud, Yina Huang

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.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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

10 authors.

Shannon L FerryDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Leena AbdullahDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Akshaya BalasubramanianDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.ORCID http://orcid.org/0000-0001-6629-8442
Elizabeth C NowakDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.ORCID http://orcid.org/0000-0001-8791-6166
Allison CarlDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Alexandrea TurnquistDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Asmaa MohamedDepartment of Microbiology, Immunology and Cancer Biology, University of Virginia Beirne B Carter Center for Immunology Research, Charlottesville, Virginia, USA.
Edward UsherwoodDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Mark SundrudDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Yina HuangDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA Yina.H.Huang@Dartmouth.edu.ORCID http://orcid.org/0000-0002-0125-9351

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 1985 to 2026
$91.3M
Sustaining Tissue Resident Memory T cellsR01CA254042 · NCI · DARTMOUTH COLLEGE · PI Yina Hsing Huang, Mary Jo Turk · 2022 to 2026
$2.6M
Activating Native Tumor Immunity with IL-33 Armored CARsR01CA271553 · NCI · DARTMOUTH COLLEGE · PI Yina Hsing Huang · 2023 to 2026
$2.3M
Deconvoluting CAR T cell heterogeneity to engineer durable antitumor protectionR01CA297297 · NCI · DARTMOUTH COLLEGE · PI Yina Hsing Huang · 2025 to 2026
$1.2M
NCI NIH HHS P30 CA023108NCI NIH HHS R01 CA254042NCI NIH HHS R01 CA271553NCI NIH HHS R01 CA297297
6 · The paper itself

Abstract

backgroundSystemic pre-conditioning prior to chimeric antigen receptor (CAR) T-cell infusion enhances engraftment and increases infiltration and activity of adoptively transferred cells within the tumor. Despite promising responses in some patients, additional strategies are needed to enhance overall efficacy of CAR T cells in patients with solid tumors. Armoring CAR T cells to express immunomodulatory cytokines can enhance treatment efficacy. In this study, we assess how systemic pre-conditioning impacts CAR T cells alone and in combination with interleukin (IL)-2 superkine (Sup2) and IL-33 cytokine armoring in the context of B16F10 melanoma.

methodsLocal and systemic pre-conditioning regimens were assessed in combination with TRP1-specific CAR T cells with or without Sup2 and IL-33 armoring in immunocompetent mice with B16F10 melanoma. CAR T-cell expansion kinetics and phenotype were evaluated with luminescence imaging, flow cytometry, and single-cell RNA sequencing.

resultsSystemically preconditioned mice treated with Sup2-IL33 CAR T cells elicited greater tumor control and extended overall survival compared with non-conditioned or locally preconditioned mice. Depletion of Sup2-IL33 CAR T cells in preconditioned mice resulted in loss of durable tumor control. While total body irradiation (TBI) increased unarmored CAR T-cell engraftment, Sup2-IL33 armoring increased tumor infiltration of effector cells over TOX+exhausted cells. RNA velocity trajectory analysis predicted divergent differentiation of tumor-infiltrating progenitor cells into either effector or exhausted T cells.

conclusionsSystemic preconditioning increased the expansion and persistence of transferred CAR T cells.TBI preconditioning in combination with cytokine armoring promoted the emergence of diverse effector phenotypes that correlated with enhanced efficacy of Sup2-IL33 CAR T cells in the context of B16F10 melanoma. Durable responsiveness and extended survival following combined therapy required continued CAR T-cell persistence despite the ability of Sup2-IL33 armoring to induce endogenous tumor immunity.

Indexed as

CD8-Positive T-LymphocytesImmunotherapy, AdoptiveInterleukin-2Interleukin-33Melanoma, ExperimentalReceptors, Chimeric AntigenAnimalsFemaleHumansMiceMice, Inbred C57BLT-Cell ExhaustionInterleukin-2Interleukin-33Receptors, Chimeric AntigenAdoptive cell therapy - ACTChimeric antigen receptor - CARMelanomaRadiotherapy/radioimmunotherapy

Identifiers

PMID42236119
PMCPMC13239385

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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.