A bispecific single-chain antibody that mediates target cell-restricted, supra-agonistic CD28 stimulation and killing of lymphoma cells
Abstract
We have previously reported that r28M, a recombinant bispecific single-chain antibody directed to a melanoma-associated proteoglycan (NG2) and the costimulatory CD28 molecule on T cells, induced T-cell activation, which resulted in tumor-cell killing. T-cell activation did not require a primary signal through the T-cell antigen receptor (TCR)/CD3 complex and depended on the presence of NG2-positive tumor cells. Here, we further investigate this phenomenon of a target cell-restricted, supra-agonistic CD28 stimulation with bispecific antibodies. To this end, we exchanged the NG2 targeting part of r28M with a single-chain antibody directed to the B-cell associated antigen CD20. The resulting bispecific single-chain antibody, termed r2820, induced supra-agonistic T-cell activation, which required the presence of autologous normal or malignant B cells, respectively. Once activated, T cells were capable of destroying lymphoma target cells.These findings demonstrate that supra-agonistic CD28 stimulation with bispecific single-chain antibodies is a robust and readily reproducible phenomenon. In the context of experimental tumor therapy, it may provide a valuable alternative to the unrestricted T-cell activation induced by 'super-agonistic', monospecific CD28 antibodies.
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The effective mode of action of rM28 was extended to cytolysis of lymphoma cells using an anti-CD28 x CD20 bispecific tandem scFv with supra-agonistic properties.
“This effective mode of action was recently extended to the cytolysis of lymphoma cells using an anti-CD28 x CD20 bispecific tandem scFv endowed with the same supra-agonistic properties. 41”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [41]
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- Authors
- Otz, T., Große-Hovest, L., Hofmann, M., Rammensee, H.-G., & Jung, G.
- Affiliations
- University of Tübingen (DE)
- Corresponding author
- Jung, G
- Venue
- Leukemia
- Published
- 2008-10-02
- Volume
- 23
- Issue
- 1
- Pages
- 71-77
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- OpenAlex
- W2051530139
- Cited by
- 38
- References
- 18
- Citations by year
- 2026: 1 · 2024: 3 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2015: 4 · 2014: 4 · 2013: 4 · 2012: 4
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Leukemia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- bispecific single-chain antibody, CD28, T cell activation, lymphoma, CD20, NG2, T cell costimulation, tumor cell killing, cancer immunotherapy
- MeSH terms
- Chondroitin Sulfate Proteoglycan 4, Antigens, Antineoplastic Agents, B-Lymphocytes, Cell Line, Cytotoxicity, Immunologic, Humans, Lymphocyte Activation, Lymphoma, Proteoglycans, T-Lymphocytes, Antibodies, Bispecific, CD28 Antigens, Jurkat Cells
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