Bi20 (fBTA05), a novel trifunctional bispecific antibody (anti‐CD20 × anti‐CD3), mediates efficient killing of B‐cell lymphoma cells even with very low CD20 expression levels
Abstract
Trifunctional bispecific antibodies can efficiently mediate tumor cell killing by redirecting T cells and immune accessory cells to the tumor cell. Here, we describe the new trifunctional antibody, Bi20 (FBTA05, anti‐CD20 × anti‐CD3), that connects B cells and T cells via its variable regions and recruits FcγRI+ accessory immune cells via its Fc region. Bi20 mediated efficient and specific lysis of B‐cell lines and of B cells with low CD20 expression levels that were derived from CLL patients. Remarkably, T‐cell activation and tumor cell killing occurred in an entirely autologous setting without additional effector cells in 5 of 8 samples. In comparison, rituximab, a chimeric monoclonal CD20 antibody, demonstrated a significantly lower B‐cell eradication rate. Additionally, Bi20, but not rituximab, upregulated the activation markers CD25 and CD69 on both CD4+ and CD8+ T cells in the presence of accessory immune cells. CD14+ accessory cells and the monocyte cell line THP‐1 were activated via binding of the Fc region of Bi20, given that T cells were simultaneously engaged by the antibody. Bi20 induced a strong Th1 cytokine pattern characterized by high IFN‐γ and very low IL‐4 secretion. In conclusion, Bi20 may offer new immunotherapeutic options for the treatment of B‐cell lymphomas. © 2008 Wiley‐Liss, Inc.
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In vitro, Bi20 mediated efficient and specific lysis of B cell lines and B cells with low CD20 expression levels derived from chronic lymphocytic leukemia patients.
“In vitro, Bi20 was shown to mediate an efficient and specific lysis of B cell lines and B cells with low CD20 expression levels that were derived from chronic lymphocytic leukemia (CLL) patients. 31”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [31]
T cell activation and tumor cell killing occurred in an entirely autologous setting, without additional effector cells, in 5 of 8 samples.
“T cell activation and tumor cell killing occurred in an entirely autologous setting, i.e., without additional effector cells, in 5 of 8 samples.”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [31]
Rituximab demonstrated a significantly lower B cell eradication rate compared to Bi20.
“In comparison, rituximab demonstrated a significantly lower B cell eradication rate. 31”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [31]
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Bispecific antibodies for cancer therapy: The light at the end of the tunnel?
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Self-citation
- Authors
- Stanglmaier, M., Faltin, M., Ruf, P., Bodenhausen, A., Schröder, P., & Lindhofer, H.
- Corresponding author
- Lindhofer, Horst
- ORCID
- Ruf, Peter
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2008-06-10
- Volume
- 123
- Issue
- 5
- Pages
- 1181-1189
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2040558969
- Cited by
- 66
- References
- 49
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 5 · 2013: 4 · 2012: 2
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- B-cell lymphoma, chronic lymphocytic leukemia, T cell redirection, Fc gamma receptor I, T cell activation, Th1 cytokine response, interferon-gamma, antibody-mediated cell lysis
- MeSH terms
- Animals, Antibody-Dependent Cell Cytotoxicity, Antineoplastic Agents, Burkitt Lymphoma, Isoelectric Focusing, Leukocytes, Mononuclear, Lymphocyte Depletion, Leukemia, Lymphocytic, Chronic, B-Cell, Gene Expression Regulation, Neoplastic, Lymphoma, B-Cell, CD3 Complex, Antibodies, Bispecific, Antigens, CD20, Cell Line, Tumor, Mice
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