ArticleThe Journal of clinical investigation2009
Monoclonal antibodies directed to CD20 and HLA-DR can elicit homotypic adhesion followed by lysosome-mediated cell death in human lymphoma and leukemia cells.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 176 citations in OpenAlex.
- Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- Article
- Lymph node microenvironment remodeling unlocks local antibody-mediated B cell depletion.Science advances · 2026Article
- Generation of anti-bovine CD20 monoclonal antibody with cytotoxic activity for the depletion of bovine B-cell lymphoma cells.Scientific reports · 2026Article
- CD20-directed antibody-drug conjugates in non-hodgkin lymphoma: translating preclinical promise into clinical reality.Journal of hematology & oncology · 2026Review
- FOXM1 down-regulation is a trigger of isatuximab-induced direct cell death in multiple myeloma cells with 1q.Haematologica · 2026Article
- Novel anti-ITGA4 monoclonal antibody induces cell death via large pore formation in NK/T-cell lymphoma cells.Scientific reports · 2025Article
- Efferocytosis: the art of cellular clearance and novel perspectives in disease therapy.Molecular cancer · 2025Review
- Neonatal-Inspired Reprogramming of Microglial Pan-Programmed Cell Death Enhances Regeneration in Adult Spinal Cord Injury.Research (Washington, D.C.) · 2025Article
- NK Cytotoxicity Mediated by NK-92 Cell Lines Expressing Combinations of Two Allelic Variants forAntibodies (Basel, Switzerland) · 2024Article
- Deregulation of New Cell Death Mechanisms in Leukemia.Cancers · 2024Review
- Update on the Application of Monoclonal Antibody Therapy in Primary Membranous Nephropathy.Drugs · 2023Review
- Direct Cell Death Induced by CD20 Monoclonal Antibodies on B Cell Lymphoma Cells Revealed by New Protocols of Analysis.Cancers · 2023Article
- Advances in antibody-based therapy in oncology.Nature cancer · 2023Review
- Stromal cell inhibition of anti-CD20 antibody mediated killing of B-cell malignancies.Frontiers in cell and developmental biology · 2023Article
- ARHGAP-RhoA signaling provokes homotypic adhesion-triggered cell death of metastasized diffuse-type gastric cancer.Oncogene · 2022Article
- Efficacy and mechanism of the anti-CD38 monoclonal antibody Daratumumab against primary effusion lymphoma.Cancer immunology, immunotherapy : CII · 2022Article
- Delay induced interaction of humoral- and cell-mediated immune responses with cancer.Theory in biosciences = Theorie in den Biowissenschaften · 2022Article
- Targeted Immunotherapy for Autoimmune Disease.Immune network · 2022Review
- The selection of variable regions affects effector mechanisms of IgA antibodies against CD20.Blood advances · 2021Article
28 more citing papers are in PubMed but not listed here.
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14 authors at 1 institution in 1 country.
Funding
Abstract
mAbs are becoming increasingly utilized in the treatment of lymphoid disorders. Although Fc-FcgammaR interactions are thought to account for much of their therapeutic effect, this does not explain why certain mAb specificities are more potent than others. An additional effector mechanism underlying the action of some mAbs is the direct induction of cell death. Previously, we demonstrated that certain CD20-specific mAbs (which we termed type II mAbs) evoke a nonapoptotic mode of cell death that appears to be linked with the induction of homotypic adhesion. Here, we reveal that peripheral relocalization of actin is critical for the adhesion and cell death induced by both the type II CD20-specific mAb tositumomab and an HLA-DR-specific mAb in both human lymphoma cell lines and primary chronic lymphocytic leukemia cells. The cell death elicited was rapid, nonapoptotic, nonautophagic, and dependent on the integrity of plasma membrane cholesterol and activation of the V-type ATPase. This cytoplasmic cell death involved lysosomes, which swelled and then dispersed their contents, including cathepsin B, into the cytoplasm and surrounding environment. The resulting loss of plasma membrane integrity occurred independently of caspases and was not controlled by Bcl-2. These experiments provide what we believe to be new insights into the mechanisms by which 2 clinically relevant mAbs elicit cell death and show that this homotypic adhesion-related cell death occurs through a lysosome-dependent pathway.
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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.