ArticleBlood advances2019
Anti-BAFF-R antibody VAY-736 demonstrates promising preclinical activity in CLL and enhances effectiveness of ibrutinib.
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
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- Advances in the treatment of systemic lupus erythematosus: Biologicals, small-molecular agents, and cell-depleting therapies coming to the clinic.Journal of internal medicine · 2026Review
- BTK-Inhibitor Loaded Polymeric Nanoparticles Alleviate Systemic Lupus Erythematosus by Targeting Elimination of Autoreactive BAFFRInternational journal of molecular sciences · 2026Article
- Addition of Ianalumab (VAY736) to Ibrutinib in Patients with Chronic Lymphocytic Leukemia on Ibrutinib Therapy: Results from a Phase Ib Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Novel immunotargets in multiple myeloma: biological relevance and therapeutic potential.Biomarker research · 2025Review
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- Causal relationship between immune cell signatures and colorectal cancer: a bi-directional, two-sample mendelian randomization study.BMC cancer · 2025Article
- Opportunities and limitations of B cell depletion approaches in SLE.Nature reviews. Rheumatology · 2025Review
- Novel Tri-Specific Immuno-Modulatory Antibody Combined with HDACi to Potentiate T Cell Activation and Anti-Tumor Efficacy.Journal of Cancer · 2025Article
- Venetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia.Blood · 2024Article
- Review
- [Research advances on B-cell activating factor and its targeted agents in inflammatory bowel disease].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Review
- An unappreciated cell survival-independent role for BAFF initiating chronic lymphocytic leukemia.Frontiers in immunology · 2024Article
- Causal relationship between immune cells and hepatocellular carcinoma: a Mendelian randomisation study.Journal of Cancer · 2024Article
- Generation of a humanized afucosylated BAFF-R antibody with broad activity against human B-cell malignancies.Blood advances · 2023Article
- The BAFF-APRIL System in Cancer.Cancers · 2023Review
- NF-kB and the CLL microenvironment.Frontiers in oncology · 2023Review
- Rituximab resistance in ITP and beyond.Frontiers in immunology · 2023Review
- The IL32/BAFF axis supports prosurvival dialogs in the lymphoma ecosystem and is disrupted by NIK inhibition.Haematologica · 2022Article
- A BAFFlingHaematologica · 2022Article
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
The Bruton tyrosine kinase inhibitor (BTKi) ibrutinib has transformed chronic lymphocytic leukemia (CLL) therapy but requires continuous administration. These factors have spurred interest in combination treatments. Unlike with chemotherapy, CD20-directed antibody therapy has not improved the outcome of BTKi treatment. Whereas CD20 antigen density on CLL cells decreases during ibrutinib treatment, the B-cell activating factor (BAFF) and its receptor (BAFF-R) remain elevated. Furthermore, BAFF signaling via noncanonical NF-κB remains elevated with BTKi treatment. Blocking BAFF interaction with BAFF-R by using VAY-736, a humanized defucosylated engineered antibody directed against BAFF-R, antagonized BAFF-mediated apoptosis protection and signaling at the population and single-cell levels in CLL cells. Furthermore, VAY-736 showed superior antibody-dependent cellular cytotoxicity compared with CD20- and CD52-directed antibodies used in CLL. VAY-736 exhibited in vivo activity as a monotherapy and, when combined with ibrutinib, produced prolonged survival compared with either therapy alone. The in vivo activity of VAY-736 is dependent upon immunoreceptor tyrosine-based activation motif (ITAM)-mediated activation of effector cells as shown by using an ITAM-deficient mouse model. Collectively, our findings support targeting the BAFF signaling pathway with VAY-736 to more effectively treat CLL as a single agent and in combination with ibrutinib.
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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.