Evidence map›Paper›PMID 41133678›Full record

ArticleAntibodies (Basel, Switzerland)2025

Novel Humanized Anti-HER3 Antibodies: Structural Characterization and Therapeutic Activity.

Alessia Muzi, Roberto Arriga, Giovanni Bulfaro, Francesca Fata, Antonella Costanzo, Valerio Chiarini, Manuela Cappelletti, Fabiana Fosca Ferrara, Federica Bucci, Linda Celeste Montemiglio and 6 more

Abstract read
In one paragraph

Article in Antibodies (Basel, Switzerland), 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

16 authors.

Alessia MuziTakis s.r.l., 00128 Rome, Italy.ORCID 0000-0001-6946-3888
Roberto ArrigaTakis s.r.l., 00128 Rome, Italy.ORCID 0000-0002-1407-7995
Giovanni BulfaroDepartment of Biochemical Sciences "Alessandro Rossi Fanelli", Sapienza University of Rome, P. le Aldo Moro, 5, 00185 Rome, Italy.ORCID 0000-0001-5289-2969
Francesca FataInstitute of Molecular Biology and Pathology, Department of Biochemical Sciences "Alessandro Rossi Fanelli", Sapienza University of Rome, National Research Council, P. le Aldo Moro, 5, 00185 Rome, Italy.ORCID 0000-0002-8412-6326
Antonella CostanzoDepartment of Biochemical Sciences "Alessandro Rossi Fanelli", Sapienza University of Rome, P. le Aldo Moro, 5, 00185 Rome, Italy.ORCID 0000-0002-9634-0063
Valerio ChiariniTakis s.r.l., 00128 Rome, Italy.
Manuela CappellettiTakis s.r.l., 00128 Rome, Italy.ORCID 0009-0000-2748-6803
Fabiana Fosca FerraraTakis s.r.l., 00128 Rome, Italy.ORCID 0009-0001-9712-8494
Federica BucciTakis s.r.l., 00128 Rome, Italy.
Linda Celeste MontemiglioInstitute of Molecular Biology and Pathology, Department of Biochemical Sciences "Alessandro Rossi Fanelli", Sapienza University of Rome, National Research Council, P. le Aldo Moro, 5, 00185 Rome, Italy.ORCID 0000-0002-4253-7493
Carmelinda SavinoInstitute of Molecular Biology and Pathology, Department of Biochemical Sciences "Alessandro Rossi Fanelli", Sapienza University of Rome, National Research Council, P. le Aldo Moro, 5, 00185 Rome, Italy.ORCID 0000-0002-1602-4838
Emanuele MarraTakis s.r.l., 00128 Rome, Italy.ORCID 0000-0001-7492-5514
Gennaro CilibertoTakis s.r.l., 00128 Rome, Italy.
Luigi AurisicchioTakis s.r.l., 00128 Rome, Italy.ORCID 0000-0003-3110-4534
Beatrice ValloneDepartment of Biochemical Sciences "Alessandro Rossi Fanelli", Sapienza University of Rome, P. le Aldo Moro, 5, 00185 Rome, Italy.
Giuseppe RoscilliTakis s.r.l., 00128 Rome, Italy.ORCID 0000-0002-0495-8668

Funding

HERCART-Fondo per la Crescita Sostenibile - "Scienze della Vita" - Accordi per l'innovazione B89J24001640005: Progetto ECS 0000024 Rome Technopole, - CUP: B83C22002820006, PNRR Missione 4 Compo-nente 2 Investimento 1.5, finanziato dall'Unione europea - NextGenerationEU B83C22002820006
6 · The paper itself

Abstract

BACKGROUND/

objectivesThe ErbB protein family plays a critical role in the progression of various solid tumors, and HER3 has been implicated in resistance mechanisms to multiple cancer therapies due to its ability to form heterodimers with other ErbB receptors, thereby activating pathways that promote tumor growth and survival. This study aimed to generate and characterize humanized monoclonal antibodies against HER3 to inhibit its function and evaluate their potential as therapeutic agents.

methodsMurine monoclonal antibodies TK-A3 and TK-A4 were humanized and tested for binding to ErbB3 and competition with neuregulin-1β (NRG). Specificity was assessed by ELISA, and epitope identified by X-ray crystallography. Downstream signaling was analyzed by western blot for phosphorylated ErbB3, Akt, and MAPK. Antitumor activity was evaluated in vitro and in a pancreatic cancer xenograft model. A toxicology study was also conducted.

resultsTK-hu A3 and TK-hu A4 bound specifically to ErbB3 without cross-reactivity to other ErbB receptors. The ErbB3-TK-hu A3 Fab structure revealed the binding epitope. Both antibodies competed with NRG, inhibiting ErbB3, Akt, and MAPK phosphorylation in a dose-dependent manner. They suppressed cancer cell survival in vitro, and TK-hu A3 significantly delayed tumor growth in vivo. The toxicology study indicated good tolerability.

conclusionsTK-hu A3 emerged as the lead candidate, showing specific HER3 targeting, strong pathway inhibition, and antitumor efficacy in vivo. Beyond standalone use, it could support novel strategies such as T-cell engagers, ADCs, CAR-T, and bispecific antibodies. These findings highlight TK-hu A3 as a promising therapy for HER3-positive, treatment-resistant cancers, meriting further development.

Indexed as

anti-tumor activityHER3 receptorhumanized antibodiestumor cell lineX-ray crystallography

Identifiers

PMID41133678
PMCPMC12550933

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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.