Evidence map›Paper›PMID 40707958›Full record

ArticleJournal of translational medicine2025

T cell-engaging CD276xCD3 bispecific antibody for treatment of endometrial cancer.

S M Greiner, J Mauermann, M S Lutz, I Hagelstein, A D Hartkopf, L Zekri, G Jung, H R Salih, M Märklin

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05999396 (First in Human Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Efficacy of the Bispecific CD276xCD3 Antibody CC-3 in Patients With Colorectal Cancer), which is not on this 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.

NCT05999396 phase1recruitingnot on this map

First in Human Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Efficacy of the Bispecific CD276xCD3 Antibody CC-3 in Patients With Colorectal Cancer

TypeinterventionalSponsorGerman Cancer Research CenterRan2024 to 2027Enrolled89ConditionsColorectal Cancer, Breast Carcinoma, Sarcoma, Penile CarcinomaArmsAdministration of CC-3
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

9 authors.

S M GreinerDepartment of Obstetrics and Gynecology, University Hospital Tuebingen, 72076, Tuebingen, Germany.ORCID 0000-0002-1378-2975
J MauermannClinical Collaboration Unit Translational Immunology, Department of Internal Medicine, University Hospital Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
M S LutzClinical Collaboration Unit Translational Immunology, Department of Internal Medicine, University Hospital Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
I HagelsteinClinical Collaboration Unit Translational Immunology, Department of Internal Medicine, University Hospital Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
A D HartkopfDepartment of Obstetrics and Gynecology, University Hospital Tuebingen, 72076, Tuebingen, Germany.
L ZekriClinical Collaboration Unit Translational Immunology, Department of Internal Medicine, University Hospital Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.
G JungGerman Cancer Consortium (DKTK), Partner Site Tuebingen, a partnership between DKFZ and University Hospital Tuebingen, 72076, Tuebingen, Germany.
H R SalihClinical Collaboration Unit Translational Immunology, Department of Internal Medicine, University Hospital Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany. Helmut.Salih@med.uni-tuebingen.de.
M MärklinClinical Collaboration Unit Translational Immunology, Department of Internal Medicine, University Hospital Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany.

Funding

Bundesministerium für Bildung und Forschung 01EJ2403ACarl-Zeiss-Stiftung P2024-02-012Deutsche Forschungsgemeinschaft MA 9302/2-1Deutsche Krebshilfe 70113496Deutsche Krebshilfe 70114180Deutsche Krebshilfe 70115833
6 · The paper itself

Abstract

backgroundEndometrial cancer ranks among the most prevalent gynecological malignancies, with a notable increase in incidence, especially among women under 40. Although most patients are diagnosed at an early stage and have an excellent prognosis, the outcome for metastatic and recurrent cases remains poor. Current treatment for advanced-stage disease includes chemotherapy, hormonal therapy and checkpoint inhibitors. The clinical response rate to immunotherapy varies depending on the molecular subtype of endometrial carcinoma. Novel immunotherapeutic strategies are needed to improve patient survival, particularly across molecular subtypes. CD276 (cluster of differentiation 276, B7-H3) is emerging as a promising immunotherapy target due to its expression across multiple tumor types. Therapeutic targeting of CD276 may enhance immune cell infiltration into the tumor site by affecting its expression on tumor cells and tumor vasculature, which addresses a critical challenge for the successful treatment of solid tumors.

methodsWe developed a novel, IgG-based CD276xCD3 bispecific antibody termed CC-3, which has demonstrated pronounced preclinical efficacy in stimulating T cell antitumor responses and is presently undergoing evaluation in a Phase I clinical trial (NCT05999396). In this study, CC-3-induced T cell activation and proliferation was analyzed using flow cytometry. We also used a LegendPlex assay to measure the secretion of cytokines and effector molecules induced by CC-3. Finally, these processes culminated in target cell lysis which was analyzed using a flow cytometry-based cytotoxicity assay.

resultsCD276 is abundantly expressed in endometrial cancer. Treatment with CC-3 activated T cells, stimulated degranulation, and induced the secretion of cytokines and effector molecules, demonstrating CC-3-mediated T cell reactivity against endometrial cancer cells. Furthermore, CC-3 promoted robust T cell proliferation and memory T cell subset formation, culminating in potent target cell lysis.

conclusionOverall, our findings highlight the potential of CC-3 for clinical evaluation as a therapeutic option for patients with endometrial cancer.

Indexed as

Antibodies, BispecificB7 AntigensEndometrial NeoplasmsT-LymphocytesCD3 ComplexCell Line, TumorCell ProliferationFemaleHumansAntibodies, BispecificB7 AntigensCD276 protein, humanCD3 ComplexBispecific antibodiesEndometrial cancerImmunotherapy

Identifiers

PMID40707958
PMCPMC12291243

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Registered trials

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.