Evidence map›Paper›PMID 42442285›Full record

ArticleBiomaterials2027

Cytokine co-presentation on targeted lipid nanoparticles enhances in vivo T cell engineering.

Milan Patel, Joseph Choy, Leonardo Cheng, Emily Ariail, Manav Jain, Sydney R Shannon, Daniel Antov, Isabella Cozzone, Xiuchun Huang, Melvin Cheng and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2027. 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

26 authors.

Milan PatelDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Joseph ChoyTranslational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Leonardo ChengDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Emily AriailDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Manav JainDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sydney R ShannonDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Daniel AntovDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Isabella CozzoneDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Xiuchun HuangDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Melvin ChengTranslational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Sixuan LiInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Jialin SunInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Dizhe YangDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jordan PopovDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Benjamin A BiggsDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christopher J ErbTranslational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA.
Brandon ChangDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tina TianDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Matthew MullaneyDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Gavin GlennInstitute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
Yining ZhuDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Tza-Huei WangDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Jordan G GreenDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Jonathan P SchneckDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jamie B SpanglerDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hai-Quan MaoDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Therapeutic and Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Translational ImmunoEngineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: hmao@jhu.edu.

Funding

TR&D Project 3P41EB028239 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI Jamie Berta Spangler · 2019 to 2026
$11.5M
Biomimetic Matrix for Ex Vivo and In Vivo Activation of T CellsR01EB029341 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI MAO, HAI-QUAN, SCHNECK, JONATHAN P · 2020 to 2023
$1.9M
Engineered Lipid Nanoparticles and Microgel Matrix to Program Th1/Th2 Immune ResponseR01CA293906 · NCI · JOHNS HOPKINS UNIVERSITY · PI Hai-Quan Mao · 2025 to 2026
$1.2M
Tri-Signal Artificial Antigen Presenting Cells for Cancer ImmunotherapyF31CA284859 · NCI · JOHNS HOPKINS UNIVERSITY · PI SHANNON, SYDNEY ROSE · 2023 to 2025
$129k
NCI NIH HHS F31 CA284859NCI NIH HHS R01 CA293906NIBIB NIH HHS P41 EB028239NIBIB NIH HHS R01 EB029341
6 · The paper itself

Abstract

T lymphocytes are attractive cellular targets for gene therapy and cell engineering, due to their critical role in adaptive immunity; however, efficient in vivo T cell transfection remains challenging. Antibody-conjugated lipid nanoparticles (LNPs) have emerged as a non-viral approach to engage T cells in vivo, but existing platforms primarily deliver activation signals 1 and 2 and lack cytokine-mediated signal 3 support. Here, we introduce a signal 3-augmented LNP design in which interleukin-7 (IL-7) is co-conjugated to the LNP surface with anti-CD3 and anti-CD28 antibodies, enabling localized tri-signal presentation at the T cell-nanoparticle interface. IL-7 co-presentation by these anti-CD3/anti-CD28/IL-7 LNPs significantly enhances particle uptake and transgene expression in primary human T cells compared to antibody-only LNPs or equivalent supplementation with soluble IL-7, demonstrating the importance of particle-bound signal 3 delivery. In naïve T cells, IL-7-conjugated LNPs promote coupled proliferation and transgene expression, increasing the fraction of transfected cells within both proliferating and non-proliferating populations. In vivo, IL-7-conjugated LNPs bias functional mRNA transfection toward splenic T cells while reducing hepatic T cell transfection, without altering overall organ-level biodistribution. As a proof of concept, IL-7-conjugated LNPs deliver chimeric antigen receptor (CAR) mRNA to generate functional CAR-expressing T cells in vivo, enabling antigen-specific target cell depletion. Together, these results establish cytokine signal 3 co-presentation as an effective design approach for T cell-targeted mRNA LNPs, resulting in enhanced engagement, uptake, and transfection in T cells in vivo.

Indexed as

Cell EngineeringCytokinesInterleukin-7LipidsNanoparticlesT-LymphocytesAnimalsCD28 AntigensHumansLiposomesMiceTransfectionCD28 AntigensCytokinesInterleukin-7Lipid NanoparticlesLipidsLiposomesCAR-T cellImmunotherapyInterleukin-7Lipid nanoparticlesmRNA

Identifiers

PMID42442285
PMCPMC13453488

What OpenQuestion holds

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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.