ArticleScience translational medicine2015
A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07243470 (A Multicenter, Open-label Phase I/II Trial Aiming to Assess the Safety and Clinical Activity of Tarlatamab in Combination With Metronomic Temozolomide in Adolescents and Adults' Patients With High Grade Brain Tumors), which is not on this map. Cited by 353 papers, 2 of them syntheses that pooled it.
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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.
A Multicenter, Open-label Phase I/II Trial Aiming to Assess the Safety and Clinical Activity of Tarlatamab in Combination With Metronomic Temozolomide in Adolescents and Adults' Patients With High Grade Brain Tumors
Who cites it
353 citing papers in PubMed, 2 syntheses or guidelines pooled it, 565 citations in OpenAlex.
- Efficacy and toxicity of lurbinectedin in subsequent systemic therapy of extensive-stage small cell lung cancer: a meta-analysis.BMC cancer · 2024Pooled it
- Knowledge atlas of antibody-drug conjugates on CiteSpace and clinical trial visualization analysis.Frontiers in oncology · 2022Pooled it
- Imaging with [The Lancet. Oncology · 2024Trial
- Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.Annals of medicine · 2026Review
- Non-conventional histologies of prostate cancer: from morphology to biology-driven precision oncology.The oncologist · 2026Review
- Tarlatamab in Relapsed SCLC With Idiopathic Pulmonary Fibrosis: A Case With Comparative DLL3 Expression Analysis: Case Report.JTO clinical and research reports · 2026Article
- Article
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
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- DLL3-Targeted Strategies in Advanced Prostate Cancer: Current Evidence and Future Perspectives.Drugs · 2026Review
- Antibody-Drug Conjugates in Lung Cancer: Promise, Progress, and Persistent Challenges.Current issues in molecular biology · 2026Review
- Emerging Therapeutic Strategies in Small-Cell Lung Cancer: From Adaptive Resistance to Precision Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Multiplexed quantitative proteomics in small-cell lung cancer: stage-linked DLL3 distribution and an independent prognostic signal of thymidine phosphorylase.Translational lung cancer research · 2026Article
- Proteomic Profiling Identifies CLDN3 as a Tumor-Selective Therapeutic Target in Small Cell Lung Cancer.bioRxiv : the preprint server for biology · 2026Article
- Nicotinic Acid Restriction Enhances the Therapeutic Benefit of NAMPT Inhibition in Small-Cell Lung Cancer Models.Cancer science · 2026Article
- Humanized antibody-drug conjugates for Somatostatin receptor 2 (SSTR2)-positive tumor treatment.Molecular cancer therapeutics · 2026Article
- Single-Cell and Spatial Transcriptomics Reframe the Immunosuppressive Microenvironment of Neuroendocrine Neoplasms.Cancers · 2026Review
- Decoding Small Cell Lung Cancer: Molecular Subtypes, Surface Antigens, and the Target-Modality Problem.Cancers · 2026Review
- Delta-like Ligand 3-DirectedJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- Landscape of T-cell bispecific antibodies in cancer therapy: therapeutic strategies, challenges and future prospection.Molecular cancer · 2026Review
293 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 3 institutions in 1 country.
Funding
Abstract
The high-grade pulmonary neuroendocrine tumors, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), remain among the most deadly malignancies. Therapies that effectively target and kill tumor-initiating cells (TICs) in these cancers should translate to improved patient survival. Patient-derived xenograft (PDX) tumors serve as excellent models to study tumor biology and characterize TICs. Increased expression of delta-like 3 (DLL3) was discovered in SCLC and LCNEC PDX tumors and confirmed in primary SCLC and LCNEC tumors. DLL3 protein is expressed on the surface of tumor cells but not in normal adult tissues. A DLL3-targeted antibody-drug conjugate (ADC), SC16LD6.5, comprised of a humanized anti-DLL3 monoclonal antibody conjugated to a DNA-damaging pyrrolobenzodiazepine (PBD) dimer toxin, induced durable tumor regression in vivo across multiple PDX models. Serial transplantation experiments executed with limiting dilutions of cells provided functional evidence confirming that the lack of tumor recurrence after SC16LD6.5 exposure resulted from effective targeting of DLL3-expressing TICs. In vivo efficacy correlated with DLL3 expression, and responses were observed in PDX models initiated from patients with both limited and extensive-stage disease and were independent of their sensitivity to standard-of-care chemotherapy regimens. SC16LD6.5 effectively targets and eradicates DLL3-expressing TICs in SCLC and LCNEC PDX tumors and is a promising first-in-class ADC for the treatment of high-grade pulmonary neuroendocrine tumors.
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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.