Evidence map›Paper›PMID 39220699›Full record

ArticleACS central science2024

Cathepsin B Nuclear Flux in a DNA-Guided "Antinuclear Missile" Cancer Therapy.

Fei Cao, Caroline Tang, Xiaoyong Chen, Zewei Tu, Ying Jin, Olivia M Turk, Robert N Nishimura, Allen Ebens, Valentina Dubljevic, James A Campbell and 2 more

Abstract read
In one paragraph

Article in ACS central science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

12 authors.

Fei CaoDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut 06510, United States.ORCID https://orcid.org/0000-0002-5385-1496
Caroline TangDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut 06510, United States.
Xiaoyong ChenDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut 06510, United States.
Zewei TuDepartment of Neurosurgery, Yale School of Medicine, New Haven, Connecticut 06510, United States.
Ying JinDivision of Vascular Surgery and Endovascular Therapy, Department of Surgery, Yale School of Medicine, New Haven, Connecticut 06510, United States.
Olivia M TurkDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut 06510, United States.
Robert N NishimuraDepartment of Research & Development, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California 90073, United States.
Allen EbensAdanate, Palo Alto, California 94305, United States.
Valentina DubljevicPatrys Ltd, Melbourne 3205, Australia.ORCID https://orcid.org/0000-0002-7944-8937
James A CampbellPatrys Ltd, Melbourne 3205, Australia.
Jiangbing ZhouDepartment of Neurosurgery, Yale School of Medicine, New Haven, Connecticut 06510, United States.ORCID https://orcid.org/0000-0002-1201-5360
James E HansenDepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut 06510, United States.ORCID https://orcid.org/0009-0002-7376-8494

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
NRSA Training CoreTL1TR001864 · NCATS · YALE UNIVERSITY · PI CANTLEY, LLOYD G, EDELMAN, E. JENNIFER · 2016 to 2025
$9.9M
Targeting Glioblastoma with a Nuclear-penetrating Anti-DNA AutoantibodyR01NS112223 · NINDS · YALE UNIVERSITY · PI James E. Hansen · 2020 to 2026
$2.4M
NCATS NIH HHS TL1 TR001864NCATS NIH HHS UL1 TR001863NINDS NIH HHS R01 NS112223
6 · The paper itself

Abstract

Some antinuclear antibodies (ANAs) bind extracellular nucleic acids released into tumor environments and are pulled into the nuclei of live cancer cells through nucleoside salvage pathways, independent of tumor-specific surface antigens. Here we show that ANA nuclear penetration induces nuclear flux by the lysosomal protease cathepsin B and leverage this mechanism to design an antinuclear antibody-drug conjugate (ANADC) with cathepsin B-labile drug linker. The ANADC targets nucleic acid exhaust from necrotic tumors and crosses membrane barriers through nucleoside salvage as a DNA-seeking and tumor agnostic "antinuclear missile" cancer therapy.

Identifiers

PMID39220699
PMCPMC11363321

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.