Evidence map›Paper›PMID 30647854›Full record

ArticleOncotarget2018

Payload of T-DM1 binds to cell surface cytoskeleton-associated protein 5 to mediate cytotoxicity of hepatocytes.

Yukinori Endo, Kazuyo Takeda, Nishant Mohan, Yi Shen, Jiangsong Jiang, David Rotstein, Wen Jin Wu

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.4field-weighted citation impact, top 15% of its field
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

25 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. A review of targeted drug delivery with antibody-drug complexes.The Journal of pharmacology and experimental therapeutics · 2025
    Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. 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

7 authors at 3 institutions in 1 country.

Yukinori EndoDivision of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, MD, USA.
Kazuyo TakedaMicroscopy and Imaging Core Facility, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, MD, USA.
Nishant MohanDivision of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, MD, USA.
Yi ShenDivision of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, MD, USA.
Jiangsong JiangDivision of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, MD, USA.
David RotsteinDivision of Compliance, Office of Surveillance and Compliance, Center for Veterinary Medicine, U.S. Food and Drug Administration (FDA), Derwood, MD, USA.
Wen Jin WuDivision of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, MD, USA.
United States Food and Drug Administration · USCenter for Drug Evaluation and Research · USCenter for Veterinary Medicine · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Off-target toxicity is a major cause of dose-limiting toxicity for antibody-drug conjugates (ADCs), mechanisms of which remain poorly understood. Here, we demonstrate that cytoskeleton-associated protein 5 (CKAP5) serves as a cell surface target for T-DM1 and that binding of T-DM1 to CKAP5 is mediated by payload (DM1). This study introduces a novel molecular mechanism of ADC payload-mediated interaction with cell surface molecules to induce cytotoxicity. Upon binding to CKAP5, T-DM1 causes cell membrane damage and leads to calcium influx into the cells, resulting in disorganized microtubule network and apoptosis. While binding of T-DM1 with HER2 is critical for killing HER2-positive tumor cells, our data suggest that cytotoxicity induced by T-DM1 interaction with CKAP5 may preferentially damage normal cells/tissues where HER2 expression is low or missing to cause off-target toxicity. This study provides molecular basis of ADC-induced off-target cytotoxicity and opens a new avenue for developing next generation of ADCs.

Indexed as

ado-trastuzumab emtansine (T-DM1)antibody-drug conjugate (ADC)cytoskeleton-associated protein 5 (CKAP5)hepatotoxicityHER2

Identifiers

PMID30647854
PMCPMC6324681
OpenAlexW2903892849

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.