ArticleJournal of medicinal chemistry2025
Legumain-Cleavable Top1i Antibody-Drug Conjugates without Self-Immolative Spacers Demonstrate Potent Antitumor Activity.
Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Evolution and recent advances in antibody-drug conjugate therapy for lung cancer: a comprehensive systematic review based on the Trialtrove database (inception to July 1, 2025).Frontiers in oncology · 2026Pooled it
- Linker Design in Antibody-Drug Conjugates: Balancing Stability and Drug Release.Pharmaceutics · 2026Review
- Targeted antibody-drug conjugates for rhabdomyosarcoma and other FGFR4-expressing cancers.Cell reports. Medicine · 2026Article
- Functional Peptide-Based Biomaterials for Pharmaceutical Application: Sequences, Mechanisms, and Optimization Strategies.Journal of functional biomaterials · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Virtually all antibody-drug conjugates employ a cleavable linker that is attached to a self-immolative spacer element. The linker and self-immolative spacer are widely known to have a dramatic influence on ADC stability, pharmacokinetics, and therapeutic efficacy. In 2021, our group described a highly polar legumain-cleavable linker that could be used to generate highly potent MMAE-based ADCs. Herein, we build on this finding by describing the design of legumain-cleavable ADCs that release a potent topoisomerase-I inhibitor (TOP1i) without the need for a self-immolative spacer. These ADCs employ an α-TROP2 antibody to target various pancreatic cancer lines. We directly compare their potency, stability, efficacy, and pharmacokinetics to an industry-standard deruxtecan comparator. We show that our TOP1i ADCs exhibit robust cytotoxicity against various cell lines, exert bystander activity, and elicit exquisite efficacy. We believe that this novel linker technology is now poised to be incorporated into next-generation ADCs for a variety of applications.
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What OpenQuestion holds
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.