ArticleJournal of translational medicine2025
Preclinical synergistic effects when combining a radiolabelled HER2-targeting single domain antibody with PARP inhibitor Olaparib.
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. Cited by 2 papers.
What it found
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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.
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.
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Who cites it
2 citing papers in PubMed.
- Antibody-Radionuclide Conjugates for Solid Tumors: Multidimensional Strategies from Component Engineering to Synergistic Combination Therapy.International journal of molecular sciences · 2026Review
- Highlight selection of radiochemistry and radiopharmacy developments by editorial board.EJNMMI radiopharmacy and chemistry · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe HER2 targeted therapy paradigm has increasingly shifted in recent years from focussed treatment of only cancers with high HER2 expression towards those with also low HER2 expression, unlocking a larger subset of patients, in either single or combination treatment strategies. Radiotherapeutic HER2-targeting single-domain antibody (sdAb) 2Rs15d has been previously developed and characterised (pre-)clinically for HER2 high-expressing tumours. The current study explores the use of [131I]I-GMIB- and [225Ac]Ac-DOTA-labelled sdAb 2Rs15d as single treatments or as combinations with the PARP-inhibitor Olaparib in HER2 low-expressing xenografts.
results[131I]I-GMIB-2Rs15d and [225Ac]Ac-DOTA-2Rs15d specifically bound to HER2-low-expressing DLD-1 BRCA2−/− cells in vitro, inflicted DNA damage (elevated γH2AX) and decreased cell viability as a single agent, an effect that was invigorated upon combination with Olaparib. Radiotracers showed specific tumour uptake in DLD-1 BRCA2−/− tumour xenografts, correlating with the low HER2 expression in this model. Clear antitumour effects were observed in mice treated with fractionated [131I]I-GMIB-2Rs15d (8 × 37 MBq, p’=0.00232) and [225Ac]Ac-DOTA-2Rs15d (8 × 20 kBq, p’=0.0149) compared to vehicle control. In combination with Olaparib (28 × 75 mg/kg), synergistic effects were observed for both [131I]I-GMIB-2Rs15d and [225Ac]Ac-DOTA-2Rs15d.
conclusion[131I]I-GMIB-2Rs15d and [225Ac]Ac-DOTA-2Rs15d showed therapeutic efficacy in tumour xenografts expressing low levels of HER2. Furthermore, when treatment was combined with Olaparib both radiopharmaceuticals prolonged survival further, underlining a synergistic effect.
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