ArticleLeukemia research2015
LFA-1-targeting Leukotoxin (LtxA; Leukothera®) causes lymphoma tumor regression in a humanized mouse model and requires caspase-8 and Fas to kill malignant lymphocytes.
Article in Leukemia research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Leveraging the active conformation of LFA-1 as a potential target for hematological malignancies.Molecular therapy. Methods & clinical development · 2025Article
- The Oral Microbiome and Cancer.Advances in experimental medicine and biology · 2025Review
- PA-MSHA exerts potent activity against cetuximab-resistant colorectal cancer through the miR-7-5p/Akt3/Wnt-β-catenin pathway.Translational cancer research · 2024Article
- Extracellular vesicles from Aggregatibacter actinomycetemcomitans exhibit potential antitumorigenic effects in oral cancer: a comparative in vitro study.Archives of microbiology · 2024Article
- Therapeutic Applications ofPathogens (Basel, Switzerland) · 2024Review
- Leukotoxin (LtxA/Leukothera) induces ATP expulsion via pannexin-1 channels and subsequent cell death in malignant lymphocytes.Scientific reports · 2021Article
- An Overview on Diffuse Large B-Cell Lymphoma Models: Towards a Functional Genomics Approach.Cancers · 2021Review
- Aggregatibacter actinomycetemcomitans leukotoxin: From mechanism to targeted anti-toxin therapeutics.Molecular oral microbiology · 2020Review
- Article
- Review
- Aggregatibacter actinomycetemcomitans Leukotoxin (LtxA) Requires Death Receptor Fas, in Addition to LFA-1, To Trigger Cell Death in T Lymphocytes.Infection and immunity · 2019Article
- Development and Significance of Mouse Models in Lymphoma Research.Current hematologic malignancy reports · 2019Review
- Article
- Role of LFA-1 and ICAM-1 in Cancer.Cancers · 2017Review
- Functional role of regulatory T cells in B cell lymphoma and related mechanisms.International journal of clinical and experimental pathology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Leukotoxin (LtxA) is a protein secreted from the oral bacterium Aggregatibacter actinomycetemcomitans. LtxA binds to the β2 integrin lymphocyte-associated function antigen-1 (LFA-1) on human white blood cells (WBCs), resulting in cell death. LtxA is currently under investigation as a novel therapy (Leukothera(®)) for treating hematologic malignancies and autoimmune diseases. We show here that LtxA has potent in vivo anti-lymphoma activity in mice. LtxA caused complete regression of B-cell tumors and promoted long-term survival of mice. The mechanism of LtxA-mediated killing of malignant lymphocytes was further examined. We found that LtxA kills malignant lymphocytes by a novel mechanism requiring the death receptor Fas and caspase-8, but not Fas ligand (FasL) or caspase-9. We also determined that LFA-1 and Fas are closely associated on the cell surface and this proximity of LFA-1 and Fas could explain how signaling through an integrin can lead to cell death. In addition to LFA-1, this work reveals a second surface protein, Fas, that is critical for LtxA-mediated cell death. Knowledge of the mechanism of cell death induced by LtxA will facilitate the development and understanding of this potent experimental therapeutic agent.
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Registered trials
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