ArticleMolecular cancer therapeutics2024
Brentuximab Vedotin-Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity.
Article in Molecular cancer therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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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
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- The efficacy and safety of Tisotumab vedotin in the treatment of recurrent/metastatic cervical cancer: a systematic review and meta-analysis of single-arm studies.Frontiers in pharmacology · 2025Pooled it
- Trial
- Nivolumab plus brentuximab vedotin for relapsed/refractory diffuse large B-cell lymphoma.Future oncology (London, England) · 2026Trial
- Phase II Open-Label Trial of Brentuximab Vedotin with Pembrolizumab in PD-1-Pretreated Metastatic Non-Small Cell Lung Cancer and Metastatic Cutaneous Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Exploring the immunological effects of antibody-drug conjugates.Nature reviews. Clinical oncology · 2026Review
- An Integrin β6-Targeted Antibody-Drug Conjugate Optimized for Intravesical Delivery to Treat Non-Muscle-Invasive Bladder Cancer.Molecular cancer therapeutics · 2026Article
- Enfortumab vedotin induces immunogenic cell death and shows enhanced preclinical antitumor activity when combined with a PD-1 inhibitor.Cell reports. Medicine · 2026Article
- Review
- Combined therapy with ALK inhibitors and a novel EGFR-targeting antibody‒drug conjugate as a strategy for ALK-rearranged non-small cell lung cancers.Oncogenesis · 2026Article
- h3B7A-LDM, a novel anti-mesothelin antibody-drug conjugate with the potential to induce antitumor immunity, shows potent efficacy against solid tumors.Journal of pharmaceutical analysis · 2026Article
- Outcomes of patients with relapsed or refractory classic Hodgkin lymphoma after frontline brentuximab vedotin.Blood cancer journal · 2026Article
- Beyond CD30: Dual-Targeting of Malignant and Regulatory T Cells by Brentuximab Vedotin Remodels the Lymphoma Microenvironment and Overcomes Resistance via BCL2 Inhibition in Mycosis Fungoides.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Real-world efficacy and safety of disitamab vedotin (RC48) plus PD-1 inhibitors in advanced urothelial carcinoma: a single-center retrospective study.Translational andrology and urology · 2026Article
- Survival Trends and Prognostic Modeling in ALK-Positive Anaplastic Large Cell Lymphoma: A Population-Based Study in the Brentuximab Vedotin Era.Cancer medicine · 2026Article
- Frontiers in Antibody-Drug Conjugates: Mechanisms, Design Innovations, and Clinical Applications in Targeted Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Innate Immune Cell Infiltration Induced by Polatuzumab Vedotin Contributes to the Antitumor Effect in Mouse Models.EJHaem · 2026Article
- Pathways of Resistance: Modern Multiple Myeloma Therapies and Overcoming Reliance on Genomic Integrity.International journal of molecular sciences · 2026Review
- Autophagy Modulates Immunogenic Cell Death in Cancer.Cancers · 2026Review
- Targeting Cytoskeleton and Cell Motility: Past and Novel Strategies for Cancer Therapy.Oncology research · 2026Review
- Inhibitors of phosphodiesterase 1 enhance paclitaxel cytotoxicity in a MDA-MB-231-derived cell line by promoting microtubule stabilization.BBA advances · 2026Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Brentuximab vedotin, a CD30-directed antibody-drug conjugate (ADC), is approved for clinical use in multiple CD30-expressing lymphomas. The cytotoxic payload component of brentuximab vedotin is monomethyl auristatin E (MMAE), a highly potent microtubule-disrupting agent. Preclinical results provided here demonstrate that treatment of cancer cells with brentuximab vedotin or free MMAE leads to a catastrophic disruption of the microtubule network eliciting a robust endoplasmic reticulum (ER) stress response that culminates in the induction of the classic hallmarks of immunogenic cell death (ICD). In accordance with the induction of ICD, brentuximab vedotin-killed lymphoma cells drove innate immune cell activation in vitro and in vivo. In the "gold-standard" test of ICD, vaccination of mice with brentuximab vedotin or free MMAE-killed tumor cells protected animals from tumor rechallenge; in addition, T cells transferred from previously vaccinated animals slowed tumor growth in immunodeficient mice. Immunity acquired from killed tumor cell vaccination was further amplified by the addition of PD-1 blockade. In a humanized model of CD30+ B-cell tumors, treatment with brentuximab vedotin drove the expansion and recruitment of autologous Epstein-Barr virus-reactive CD8+ T cells potentiating the activity of anti-PD-1 therapy. Together, these data support the ability of brentuximab vedotin and MMAE to drive ICD in tumor cells resulting in the activation of antigen-presenting cells and augmented T-cell immunity. These data provide a strong rationale for the clinical combination of brentuximab vedotin and other MMAE-based ADCs with checkpoint inhibitors.
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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.