Evidence map›Paper›PMID 38467634›Full record

ArticleNature communications2024

Delivery of a BET protein degrader via a CEACAM6-targeted antibody-drug conjugate inhibits tumour growth in pancreatic cancer models.

Youya Nakazawa, Masayuki Miyano, Shuntaro Tsukamoto, Hiroyuki Kogai, Akihiko Yamamoto, Kentaro Iso, Satoshi Inoue, Yoshinobu Yamane, Yuki Yabe, Hirotatsu Umihara and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

26 citing papers in PubMed, 22 citations in OpenAlex.

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  18. A unified framework for identification of cell-type-specific spatially variable genes in spatial transcriptomic studies.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

18 authors at 2 institutions in 1 country.

Youya Nakazawa *Tsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan. youya.nakazawa1216@gmail.com.ORCID 0000-0003-1385-5457
Masayuki Miyano *Tsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Shuntaro TsukamotoTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Hiroyuki KogaiTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.ORCID 0009-0002-7896-3328
Akihiko YamamotoTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Kentaro IsoTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.ORCID 0000-0001-5417-3642
Satoshi InoueTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Yoshinobu YamaneTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Yuki YabeTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Hirotatsu UmiharaTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Junichi TaguchiTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Tsuyoshi AkagiTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Atsumi YamaguchiTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Minaho KogaTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Kohta ToshimitsuTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Toshifumi HirayamaKAN Research Institute, Inc., Kobe, Japan.
Yohei MukaiKAN Research Institute, Inc., Kobe, Japan.ORCID 0000-0003-4288-4062
Akihito MachinagaTsukuba Research Laboratory, Eisai Co., Ltd., Ibaraki, Japan.
Eisai (Japan) · JPKAN Research Institute · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all cancers. To improve PDAC therapy, we establish screening systems based on organoid and co-culture technologies and find a payload of antibody-drug conjugate (ADC), a bromodomain and extra-terminal (BET) protein degrader named EBET. We select CEACAM6/CD66c as an ADC target and developed an antibody, #84.7, with minimal reactivity to CEACAM6-expressing normal cells. EBET-conjugated #84.7 (84-EBET) has lethal effects on various PDAC organoids and bystander efficacy on CEACAM6-negative PDAC cells and cancer-associated fibroblasts. In mouse studies, a single injection of 84-EBET induces marked tumor regression in various PDAC-patient-derived xenografts, with a decrease in the inflammatory phenotype of stromal cells and without significant body weight loss. Combination with standard chemotherapy or PD-1 antibody induces more profound and sustained regression without toxicity enhancement. Our preclinical evidence demonstrates potential efficacy by delivering BET protein degrader to PDAC and its microenvironment via CEACAM6-targeted ADC.

Indexed as

Carcinoma, Pancreatic DuctalImmunoconjugatesPancreatic NeoplasmsAnimalsAntigens, CDCell Adhesion MoleculesCell Line, TumorGPI-Linked ProteinsHumansMiceTumor MicroenvironmentAntigens, CDCEACAM6 protein, humanCell Adhesion MoleculesGPI-Linked ProteinsImmunoconjugates

Identifiers

PMID38467634
PMCPMC10928091
OpenAlexW4392643092

What OpenQuestion holds

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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.