Supraagonistic, bispecific single‐chain antibody purified from the serum of cloned, transgenic cows induces T‐cell‐mediated killing of glioblastoma cells in vitro and in vivo
Open accessAbstract
Here we characterize the antitumor activity of a recombinant bispecific single‐chain antibody isolated from the serum of cloned transgenic cows. The antibody, termed r28M, is directed to a melanoma‐associated proteoglycan, also expressed on glioblastoma cells, and to human CD28. Bound to tumor cells, r28M induced exceedingly efficient supraagonistic T‐cell activation via the CD28 molecule without an additional stimulus via the TCR/CD3 complex. In vitro, T cells and NK cells contributed to tumor cell killing after r28M‐mediated activation of peripheral blood mononuclear cells. However, NK activity depended on T‐cell‐derived cytokines. In vivo, r28M markedly inhibited the growth of human glioblastoma cells in nude mice. The serum half‐life of the protein after i.v. injection was approximately 6 hr. Thus, r28M is unique not only in inducing supraagonistic CD28‐mediated T‐cell activation against tumor cells in vitro and in vivo, it also meets 2 additional requirements that are critical for clinical application: a relatively long serum half‐life and the possibility of obtaining large amounts of active material from cloned transgenic livestock. © 2005 Wiley‐Liss, Inc.
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Unlike TGN1412, supra-agonistic CD28 stimulation by rM28 was strictly target-cell restricted over a wide concentration range, i.e., not induced if NG2-expressing target cells are absent.
“Indeed, unlike the activity of TGN1412, supra-agonistic CD28 stimulation by rM28 was shown to be strictly target-cell restricted over a wide concentration range, i.e., not induced if NG2-expressing target cells are absent. 43”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [43]
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- Authors
- Grosse‐Hovest, L., Wick, W., Minoia, R., Weller, M., Rammensee, H., Brem, G., & Jung, G.
- Affiliations
- University of Tübingen (DE)
- University of Bari Aldo Moro (IT)
- University of Veterinary Medicine Vienna (AT)
- Corresponding author
- Jung, Gundram
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2005-07-07
- Volume
- 117
- Issue
- 6
- Pages
- 1060-1064
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2003238375
- Cited by
- 23
- References
- 12
- Citations by year
- 2021: 1 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 2
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- Wilhelm Sander-Stiftung
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- bispecific single-chain antibody, CD28, glioblastoma, transgenic cows, recombinant antibodies, T cell cytotoxicity, NK cell cytotoxicity, serum half-life, tumor growth inhibition, transgenic livestock
- MeSH terms
- Animals, Antigens, Neoplasm, Cattle, Cell Division, Glioblastoma, Humans, Killer Cells, Natural, Kinetics, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Nude, Neoplasm Transplantation, Proteoglycans, T-Lymphocytes, Antibodies, Bispecific, CD28 Antigens, Animals, Genetically Modified, Mice
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