Evidence map›Paper›PMID 40970352›Full record

ArticleOncology reports2025

Novel tetravalent bispecific antibody, PSMA/TRAIL‑R2 REGULGENT™, induces selective tumor cell apoptosis without hepatotoxicity.

Makoto Nakayama, Sayaka Takagi-Maeda, Yusuke Machino, Kaito Nihira, Miho Inoue, Nobuaki Takahashi, Katsuaki Usami

Abstract read
In one paragraph

Article in Oncology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Makoto Nakayama *Core Research Laboratories, Bio‑Pharmaceutical Center, Research Division, Kyowa Kirin Co., Ltd., Tokyo 194‑8533, Japan.
Sayaka Takagi-Maeda *Project and Product Management Group 3, CMC Development, Manufacturing, Kyowa Kirin Co., Ltd., Tokyo 100‑0004, Japan.
Yusuke MachinoProject and Product Management Group 3, CMC Development, Manufacturing, Kyowa Kirin Co., Ltd., Tokyo 100‑0004, Japan.
Kaito NihiraGlobal Operational Transformation Kyowa Kirin International Plc., Marlow SL7 1HZ, UK.
Miho InoueInnovation Center, Research Division, Kyowa Kirin Co., Ltd., Tokyo 194‑8533, Japan.
Nobuaki TakahashiInnovation Center, Research Division, Kyowa Kirin Co., Ltd., Tokyo 194‑8533, Japan.
Katsuaki UsamiInnovation Center, Research Division, Kyowa Kirin Co., Ltd., Tokyo 194‑8533, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor necrosis factor‑related apoptosis‑inducing ligand‑receptor 2 (TRAIL‑R2) can induce apoptosis in various tumors through the oligomerization of TRAIL. Several TRAIL‑R2 agonistic monoclonal antibodies have been tested in clinical trials but have failed owing to a lack of efficacy or severe hepatotoxicity. Although bispecific constructs have been developed to improve TRAIL‑R2 targeting and enhance efficacy against tumors while reducing adverse effects on hepatocytes, the risk of hepatotoxicity still persists. The present study used a TRAIL‑R2 antibody, E11, that does not trigger apoptosis in the absence of crosslinking and constructed a novel tetravalent bispecific IgG4‑based antibody, REGULGENT™, comprised of E11 and a clone that binds to prostate‑specific membrane antigen (PSMA), a specific marker for prostate tumors. PSMA/TRAIL‑R2 REGULGENT™ selectively induced death in PSMA/TRAIL‑R2 double‑positive cells but not in TRAIL‑R2 single‑positive cells

Indexed as

Antibodies, BispecificAntigens, SurfaceGlutamate Carboxypeptidase IIProstatic NeoplasmsReceptors, TNF-Related Apoptosis-Inducing LigandAnimalsApoptosisCell Line, TumorHumansMaleMiceXenograft Model Antitumor AssaysAntibodies, BispecificAntigens, SurfaceFOLH1 protein, humanGlutamate Carboxypeptidase IIReceptors, TNF-Related Apoptosis-Inducing LigandTNFRSF10B protein, humanapoptosisno hepatotoxicityprostate‑specific membrane antigentetravalent bispecific antibodytumor necrosis factor‑related apoptosis‑inducing ligand‑receptor 2

Identifiers

PMID40970352
PMCPMC12456122

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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.