ArticleMolecular cancer therapeutics2026
Development of Antibody-Drug Conjugates Targeting L1CAM to Treat Metastatic Cancer.
Article in Molecular cancer therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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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.
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Who cites it
1 citing paper in PubMed.
- L1CAM signaling through planar cell polarity drives SOX2 expression and lung adenocarcinoma metastasis.Nature communications · 2026Article
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12 authors.
Funding
Abstract
Effective treatment for metastatic cancer has remained elusive because of the persistence of drug-resistant metastasis stem cells (MetSC) that drive relapse. MetSCs are tumor cell subpopulations enriched for their ability to reinitiate and sustain metastatic growth, displaying phenotypic plasticity and resistance to chemotherapy. These cells express the L1 cell adhesion molecule (L1CAM), a transmembrane protein detected in numerous human solid tumor types and at multiple disseminated organ sites. As a selective surface marker of MetSCs, L1CAM is a promising candidate for molecularly targeted drugs aimed at eliminating metastases, yet strategies to date have not achieved clinical success. In this study, we develop antibody-drug conjugates (ADC) to deliver highly toxic PNU-159682 payloads to L1CAM-expressing cells. We report the generation of monoclonal antibodies (mAb) with high binding affinity, specificity, and selectivity for the human L1CAM extracellular domain. Optimized L1CAM-targeting mAbs were conjugated to PNU-159682 to generate ADC variants with both cleavable and noncleavable linkers, with an average drug-antibody ratio of four. ADCs derived from three antibodies targeting various epitopes of the L1CAM extracellular portion potently killed cells exhibiting varying levels of surface L1CAM expression. L1CAM ADCs given as monotherapy resulted in robust tumor control and extended survival in mice harboring subcutaneous L1CAM+ xenografts or L1CAM+ lung metastases from triple-negative basal breast cancer and lung adenocarcinoma. Safety analyses with mouse cross-reactive antibodies indicate a feasible therapeutic window. Our findings offer strong proof of concept to support the preclinical development of these novel L1CAM ADCs as therapeutic agents for advanced solid tumors.
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