ArticleHaematologica2022
Inhibitors of ADAM10 reduce Hodgkin lymphoma cell growth in 3D microenvironments and enhance brentuximab-vedotin effect.
Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Biomimetic Scaffold-Based 3D Models for Decoding Cancer Biology and Advancing Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Monoclonal Antibodies and Derivatives: Therapeutic Tools for Cancer.Oncology research · 2026Review
- Developing a 3D Model Culture of an EBV+/CD30+ B-Anaplastic Large Cell Lymphoma Cell Line to Assay Brentuximab Vedotin Treatment.Antibodies (Basel, Switzerland) · 2025Article
- ADAM Proteases in Cancer: Biological Roles, Therapeutic Challenges, and Emerging Opportunities.Cancers · 2025Review
- Antibody-Drug Conjugates Targeting CD30 in T-Cell Lymphomas: Clinical Progression and Mechanism.Cancers · 2025Review
- Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights.Experimental hematology & oncology · 2025Review
- Article
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- Identification ofInternational journal of molecular sciences · 2023Article
- Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives.Molecules (Basel, Switzerland) · 2023Review
- ADAM10-a "multitasker" in sepsis: focus on its posttranslational target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Mechanism of action and therapeutic targeting of CD30 molecule in lymphomas.Frontiers in oncology · 2023Review
- ADAM10 and ADAM17-Novel Players in Retinoblastoma Carcinogenesis.International journal of molecular sciences · 2022Article
- 3D Models as a Tool to Assess the Anti-Tumor Efficacy of Therapeutic Antibodies: Advantages and Limitations.Antibodies (Basel, Switzerland) · 2022Review
- Current and Emerging Approaches to Study Microenvironmental Interactions and Drug Activity in Classical Hodgkin Lymphoma.Cancers · 2022Review
- Lysyl-Oxidase Dependent Extracellular Matrix Stiffness in Hodgkin Lymphomas: Mechanical and Topographical Evidence.Cancers · 2022Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Shedding of ADAM10 substrates, like TNFa or CD30, can affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. We have published two new ADAM10 inhibitors, LT4 and MN8 able to prevent such shedding in Hodgkin lymphoma (HL). Since tumor tissue architecture deeply influences the outcome of anti-cancer treatments, we set up a new threedimensional (3D) culture systems to verify whether ADAM10 inhibitors can contribute to, or enhance, the anti-lymphoma effects of the ADC brentuximab-vedotin (BtxVed). In order to recapitulate some aspects of lymphoma structure and architecture, we assembled two 3D culture models: mixed spheroids made of HL lymph node (LN) mesenchymal stromal cells (MSC) and Reed Sternberg/Hodgkin lymphoma cells (HL cells) or collagen scaffolds repopulated with LN-MSC and HL cells. In these 3D systems we found that: i) the ADAM10 inhibitors LT4 and MN8 reduce ATP content or glucose consumption, related to cell proliferation, increasing lactate dehydrogenase release as a cell damage hallmark; ii) these events are paralleled by mixed spheroids size reduction and inhibition of CD30 and TNFa shedding; iii) the effects observed can be reproduced in repopulated HL LN-derived matrix or collagen scaffolds; iv) ADAM10 inhibitors enhance the anti-lymphoma effect of the anti-CD30 ADC BtxVed both in conventional cultures and in repopulated scaffolds. Thus, we provide evidence for a direct and combined antilymphoma effect of ADAM10 inhibitors with BtxVed, leading to the improvement of ADC effects; this is documented in 3D models recapitulating features of the LN microenvironment, that can be proposed as a reliable tool for anti-lymphoma drug testing.
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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.