ArticleBlood2018
A CD19/CD3 bispecific antibody for effective immunotherapy of chronic lymphocytic leukemia in the ibrutinib era.
Article in Blood, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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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.
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Who cites it
73 citing papers in PubMed, 107 citations in OpenAlex.
- BTK inhibitors, irrespective of ITK inhibition, increase efficacy of a CD19/CD3-bispecific antibody in CLL.Blood · 2021Trial
- scFv-based biologics in diabetes: from therapeutic potential to clinical prospects.Frontiers in immunology · 2026Review
- Non-Malignant T Cells as Determinants of Immunotherapeutic Response in Chronic Lymphocytic Leukemia: Towards Personalized Strategies.Oncology research · 2026Review
- Engineering multi-specific nano-antibodies for cancer immunotherapy.Nature biomedical engineering · 2025Article
- Proteogenomic characterization of invasive breast tumors in young women.NPJ breast cancer · 2025Article
- The Role of Tumor Microenvironment and Targeted Therapy in Chronic Lymphocytic Leukemia.Current issues in molecular biology · 2025Review
- Resistance mechanisms and approach to chronic lymphocytic leukemia after BTK inhibitor therapy.Leukemia & lymphoma · 2025Review
- Beyond BCL2 (B cell lymphoma) and BTK (Bruton tyrosine kinase) inhibitors: novel agents and resistance mechanisms for chronic lymphocytic leukemia.Discover oncology · 2025Review
- Article
- Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy.American journal of hematology · 2025Review
- Leveraging the Immunomodulatory Potential of Ibrutinib for Improved Outcomes of T Cell-Mediated Therapies of B Cell Malignancies: A Narrative Review.Targeted oncology · 2025Review
- A question of TiME: how microenvironmental interactions shape response to immunotherapy in CLL and Richter Transformation.Frontiers in immunology · 2025Review
- Ibrutinib enhances the bias of T cell responses towards staphylococcal superantigens sustaining inflammation in chronic lymphocytic leukaemia.Frontiers in immunology · 2025Article
- Relapsed/refractory CLL: the role of allo-SCT, CAR-T, and T-cell engagers.Hematology. American Society of Hematology. Education Program · 2024Review
- A novel bispecific T-cell engager using the ligand-target csGRP78 against acute myeloid leukemia.Cellular and molecular life sciences : CMLS · 2024Article
- Macrophage-engaging peptidic bispecific antibodies (pBsAbs) for immunotherapyChemical science · 2024Article
- New pharmacodynamic parameters linked with ibrutinib responses in chronic lymphocytic leukemia: Prospective study in real-world patients and mathematical modeling.PLoS medicine · 2024Observational
- Siglec-6 as a therapeutic target for cell migration and adhesion in chronic lymphocytic leukemia.Nature communications · 2024Article
- Isolation of B Cells Using Silane-Coated Magnetic Nanoparticles.International journal of biomaterials · 2024Article
- Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.Acta pharmaceutica Sinica. B · 2023Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
The Bruton tyrosine kinase inhibitor ibrutinib induces high rates of clinical response in chronic lymphocytic leukemia (CLL). However, there remains a need for adjunct treatments to deepen response and to overcome drug resistance. Blinatumomab, a CD19/CD3 bispecific antibody (bsAb) designed in the BiTE (bispecific T-cell engager) format, is approved by the US Food and Drug Administration for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Because of its short half-life of 2.1 hours, blinatumomab requires continuous intravenous dosing for efficacy. We developed a novel CD19/CD3 bsAb in the single-chain Fv-Fc format (CD19/CD3-scFv-Fc) with a half-life of ∼5 days. In in vitro experiments, both CD19/CD3-scFv-Fc and blinatumomab induced >90% killing of CLL cells from treatment-naïve patients. Antileukemic activity was associated with increased autologous CD8 and CD4 T-cell proliferation, activation, and granzyme B expression. In the NOD/SCID/IL2Rγnull patient-derived xenograft mouse model, once-weekly treatment with CD19/CD3-scFv-Fc eliminated >98% of treatment-naïve CLL cells in blood and spleen. By contrast, blinatumomab failed to induce a response, even when administered daily. We next explored the activity of CD19/CD3-scFv-Fc in the context of ibrutinib treatment and ibrutinib resistance. CD19/CD3-scFv-Fc induced more rapid killing of CLL cells from ibrutinib-treated patients than those from treatment-naïve patients. CD19/CD3-scFv-Fc also demonstrated potent activity against CLL cells from patients with acquired ibrutinib-resistance harboring
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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.