Evidence map›Paper›PMID 36884217›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023

Preclinical Efficacy of the Antibody-Drug Conjugate CLDN6-23-ADC for the Treatment of CLDN6-Positive Solid Tumors.

Martina S J McDermott, Neil A O'Brien, Benjamin Hoffstrom, KeWei Gong, Ming Lu, Jun Zhang, Tong Luo, Min Liang, Weiping Jia, Jenny J Hong and 10 more

Open access · hybridAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
8.6field-weighted citation impact, top 2% 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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Targeting claudins in cancer.Nature reviews. Drug discovery · 2026
    Review
  9. Review
  10. Tight junction structure, assembly and (dys)function.Nature reviews. Molecular cell biology · 2026
    Review
  11. Article
  12. Review
  13. Antibody-Drug Conjugates in Gynecologic Oncology: Advances, Challenges, and Future Directions.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  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

20 authors at 3 institutions in 1 country.

Martina S J McDermottDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0001-5737-7202
Neil A O'BrienDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0001-7408-1091
Benjamin HoffstromDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0002-7469-3028
KeWei GongDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0002-3890-3761
Ming LuDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0003-1574-9850
Jun ZhangDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0001-6049-0572
Tong LuoDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0001-5382-7448
Min LiangDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0002-9740-7688
Weiping JiaDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0003-4662-2529
Jenny J HongDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0003-3375-9614
Kevin ChauDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0001-9945-9169
Simon DavenportPathology, University of Southern California, Los Angeles, California.ORCID 0000-0002-4860-7472
Bin XiePathology, University of Southern California, Los Angeles, California.ORCID 0000-0002-4470-0602
Michael F PressPathology, University of Southern California, Los Angeles, California.ORCID 0000-0003-3400-6614
Richard PanayiotouDepartment of Cell Biology and Ludwig Center at Harvard, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-2603-4685
Abram Handly-SantanaDepartment of Cell Biology and Ludwig Center at Harvard, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5744-1304
Joan S BruggeDepartment of Cell Biology and Ludwig Center at Harvard, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-2547-4814
Leonard PrestaDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0002-7871-1991
John GlaspyDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0002-1800-9076
Dennis J SlamonDepartment of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.ORCID 0000-0002-6330-498X
University of California, Los Angeles · USHarvard University · USUniversity of Southern California · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
NCI NIH HHS P30 CA016042
6 · The paper itself

Abstract

purposeClaudin-6 (CLDN6) is expressed at elevated levels in multiple human cancers including ovarian and endometrial malignancies, with little or no detectable expression in normal adult tissue. This expression profile makes CLDN6 an ideal target for development of a potential therapeutic antibody-drug conjugate (ADC). This study describes the generation and preclinical characterization of CLDN6-23-ADC, an ADC consisting of a humanized anti-CLDN6 monoclonal antibody coupled to monomethyl auristatin E (MMAE) via a cleavable linker. EXPERIMENTAL

designA fully humanized anti-CLDN6 antibody was conjugated to MMAE resulting in the potential therapeutic ADC, CLDN6-23-ADC. The antitumor efficacy of CLDN6-23-ADC was assessed for antitumor efficacy in CLDN6-positive (CLDN6+) and -negative (CLDN6-) xenografts and patient-derived xenograft (PDX) models of human cancers.

resultsCLDN6-23-ADC selectively binds to CLDN6, versus other CLDN family members, inhibits the proliferation of CLDN6+ cancer cells in vitro, and is rapidly internalized in CLDN6+ cells. Robust tumor regressions were observed in multiple CLDN6+ xenograft models and tumor inhibition led to markedly enhanced survival of CLDN6+ PDX tumors following treatment with CLDN6-23-ADC. IHC assessment of cancer tissue microarrays demonstrate elevated levels of CLDN6 in 29% of ovarian epithelial carcinomas. Approximately 45% of high-grade serous ovarian carcinomas and 11% of endometrial carcinomas are positive for the target.

conclusionsWe report the development of a novel ADC, CLDN6-23-ADC, that selectively targets CLDN6, a potential onco-fetal-antigen which is highly expressed in ovarian and endometrial cancers. CLDN6-23-ADC exhibits robust tumor regressions in mouse models of human ovarian and endometrial cancers and is currently undergoing phase I study.

Indexed as

Endometrial NeoplasmsImmunoconjugatesAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCell Line, TumorClaudinsDisease Models, AnimalFemaleHumansMiceXenograft Model Antitumor AssaysAntibodies, MonoclonalAntibodies, Monoclonal, Humanizedclaudin 6ClaudinsImmunoconjugates

Identifiers

PMID36884217
PMCPMC10233360
OpenAlexW4323535430

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.