Evidence map›Paper›PMID 41491256›Full record

ArticleNature biotechnology2026

Engineering bispecific exosome activators of T cells to target immune checkpoint inhibitor-resistant metastatic melanoma.

Shuo Liu, Mengrui Liu, Zhenzhen Wang, Shiqi Hu, Kaiyue Zhang, Chao Lu, Xiao Cheng, Ming Shen, Jianing Bi, Dashuai Zhu and 1 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. 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

11 authors.

Shuo Liu *Department of Biomedical Engineering, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0002-2969-5876
Mengrui Liu *Department of Biomedical Engineering, Columbia University, New York, NY, USA.
Zhenzhen Wang *Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill/Raleigh, NC, USA.
Shiqi HuDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0002-8570-3439
Kaiyue ZhangDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0002-9906-9053
Chao LuDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Xiao ChengDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Ming ShenDepartment of Biomedical Engineering, Columbia University, New York, NY, USA.
Jianing BiDepartment of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA.
Dashuai ZhuDepartment of Biomedical Engineering, Columbia University, New York, NY, USA. dz2551@columbia.edu.ORCID http://orcid.org/0000-0002-4645-5786
Ke ChengDepartment of Biomedical Engineering, Columbia University, New York, NY, USA. ke.cheng@columbia.edu.ORCID http://orcid.org/0000-0001-8053-7059

Funding

Harnessing Platelet-Endothelial Interactions for Stem Cell DeliveryR01HL144002 · NHLBI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI Ke Cheng · 2019 to 2026
$4.5M
Modulating Exosome Cargos and Surfaces for Precision Heart RepairR01HL146153 · NHLBI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI Ke Cheng · 2019 to 2026
$4.2M
Drug Delivery and Biomimetic Approaches for Optimal Stem Cell TherapyR01HL154154 · NHLBI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI CHENG, KE · 2021 to 2024
$3.1M
Inhalable stem cell exosome therapy for cardiac injuryR01HL170612 · NHLBI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Ke Cheng · 2024 to 2026
$2.2M
Sorting high extracellular vesicle secretors for optimal cell therapyR01HL179818 · NHLBI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Ke Cheng, Dino Di Carlo · 2025 to 2026
$1.4M
American Heart Association (American Heart Association, Inc.) 24CDA1277521NHLBI NIH HHS R01 HL144002NHLBI NIH HHS R01 HL146153NHLBI NIH HHS R01 HL154154NHLBI NIH HHS R01 HL170612NHLBI NIH HHS R01 HL179818U.S. Department of Health Human Services | National Institutes of Health (NIH) HL144002U.S. Department of Health Human Services | National Institutes of Health (NIH) HL146153U.S. Department of Health Human Services | National Institutes of Health (NIH) HL154154U.S. Department of Health Human Services | National Institutes of Health (NIH) HL170612U.S. Department of Health Human Services | National Institutes of Health (NIH) HL179818
6 · The paper itself

Abstract

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) is often limited by an immunosuppressive tumor microenvironment (TME). Simultaneous targeting of the TME and immune checkpoints is a promising approach to address this limitation. Here we develop an inhalable exosome system that enables co-display of two inhibitory ligands and apply it to treat lung metastases of ICI-resistant melanoma. As immune exclusion in this context is often mediated by Wnt/β-catenin signaling, we harnessed the Alix sorting domain for tandem display of PD-1 and FZD8 to block PD-L1 and Wnt7b, which is overexpressed in ICI-resistant melanoma. This technology, called bispecific exosome activator of T cells (BEAT), enables uniform 1:1 co-display of two proteins on the exosome surface. We show that BEAT concurrently recruits and activates CD8⁺ T cells to reprogram the TME, yielding robust antitumor activity in ICI-resistant melanoma mouse models. Inhaled BEAT outperforms linked dual antibody targeting PD-L1 and Wnt7b in vivo. This approach to tandem protein display may be applicable to diverse ICI-resistant cancers.

Identifiers

PMID41491256
PMCPMC13181740

What OpenQuestion holds

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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.