ArticlemAbs2015
A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells for the potent lysis of CD19(+) tumor cells.
Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- Bispecific Antibodies: From Research to Clinical Application.Frontiers in immunology · 2021Pooled it
- Functional Characteristics Derived from the Structural Design of Bispecific Antibodies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Bispecific Antibodies in Hematologic Malignancies: Attacking the Frontline.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Fragment-Based Immune Cell Engager Antibodies in Treatment of Cancer, Infectious and Autoimmune Diseases: Lessons and Insights from Clinical and Translational Studies.Antibodies (Basel, Switzerland) · 2025Review
- Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.International journal of biological sciences · 2025Review
- Engaging T cells for cleanup.Frontiers in immunology · 2025Review
- Bispecific and multispecific antibodies in oncology: opportunities and challenges.Nature reviews. Clinical oncology · 2024Review
- T-Cell Engagers-The Structure and Functional Principle and Application in Hematological Malignancies.Cancers · 2024Review
- Design and engineering of bispecific antibodies: insights and practical considerations.Frontiers in bioengineering and biotechnology · 2024Review
- Article
- End-to-end approach for the characterization and control of product-related impurities in T cell bispecific antibody preparations.International journal of pharmaceutics: X · 2023Article
- Immunotherapy in hematologic malignancies: achievements, challenges and future prospects.Signal transduction and targeted therapy · 2023Review
- [Clinical advances in bispecific antibodies for hematological malignancies].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023Article
- A high throughput bispecific antibody discovery pipeline.Communications biology · 2023Article
- Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies.Trials · 2023Article
- Immobilization-Free Binding and Affinity Characterization of Higher Order Bispecific Antibody Complexes Using Size-Based Microfluidics.Analytical chemistry · 2022Article
- Therapeutic Advances in Immunotherapies for Hematological Malignancies.International journal of molecular sciences · 2022Review
- Antibody variable region engineering for improving cancer immunotherapy.Cancer communications (London, England) · 2022Review
- Bispecific Antibody-Based Immune-Cell Engagers and Their Emerging Therapeutic Targets in Cancer Immunotherapy.International journal of molecular sciences · 2022Review
- Monoclonal Antibodies in the Treatment of Diffuse Large B-Cell Lymphoma: Moving beyond Rituximab.Cancers · 2022Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To harness the potent tumor-killing capacity of T cells for the treatment of CD19(+) malignancies, we constructed AFM11, a humanized tetravalent bispecific CD19/CD3 tandem diabody (TandAb) consisting solely of Fv domains. The molecule exhibits good manufacturability and stability properties. AFM11 has 2 binding sites for CD3 and 2 for CD19, an antigen that is expressed from early B cell development through differentiation into plasma cells, and is an attractive alternative to CD20 as a target for the development of therapeutic antibodies to treat B cell malignancies. Comparison of the binding and cytotoxicity of AFM11 with those of a tandem scFv bispecific T cell engager (BiTE) molecule targeting the same antigens revealed that AFM11 elicited more potent in vitro B cell lysis. Though possessing high affinity to CD3, the TandAb mediates serial-killing of CD19(+) cells with little dependence of potency or efficacy upon effector:target ratio, unlike the BiTE. The advantage of the TandAb over the BiTE was most pronounced at lower effector:target ratios. AFM11 mediated strictly target-dependent T cell activation evidenced by CD25 and CD69 induction, proliferation, and cytokine release, notwithstanding bivalent CD3 engagement. In a NOD/scid xenograft model, AFM11 induced dose-dependent growth inhibition of Raji tumors in vivo, and radiolabeled TandAb exhibited excellent localization to tumor but not to normal tissue. After intravenous administration in mice, half-life ranged from 18.4 to 22.9 h. In a human ex vivo B-cell chronic lymphocytic leukemia study, AFM11 exhibited substantial cytotoxic activity in an autologous setting. Thus, AFM11 may represent a promising therapeutic for treatment of CD19(+) malignancies with an advantageous safety risk profile and anticipated dosing regimen.
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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.