The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity.
Open accessAbstract
Construction of a bispecific single-chain antibody derivative is described that consists of two different single-chain Fv fragments joined through a Gly-Ser linker. One specificity of the two Fv fragments is directed against the CD3 antigen of human T cells and the other is directed against the epithelial 17-1A antigen; the latter had been found in a clinical trial to be a suitable target for antibody therapy of minimal residual colorectal cancer. The construct could be expressed in CHO cells as a fully functional protein, while its periplasmic expression in Escherichia coli resulted in a nonfunctional protein only. The antigen-binding properties of the bispecific single-chain antibody are indistinguishable from those of the corresponding univalent single-chain Fv fragments. By redirecting human peripheral T lymphocytes against 17-1A-positive tumor cells, the bispecific antibody proved to be highly cytotoxic at nanomolar concentrations as demonstrated by 51Cr release assay on various cell lines. The described bispecific construct has a molecular mass of 60 kDa and can be easily purified by its C-terminal histidine tail on a Ni-NTA chromatography column. As bispecific antibodies have already been shown to be effective in vivo in experimental tumor systems as well as in phase-one clinical trials, the small CD3/17-1A-bispecific antibody may be more efficacious than intact antibodies against minimal residual cancer cells.
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“This new kind of bsAb proved to be highly cytotoxic at nanomolar concentrations against various cell lines, using unstimulated human PBMCs in the absence of co-signaling. 44”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [44]
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Cited by
Sorted by citations
Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody
Bargou, R., Leo, E., Zugmaier, G., Klinger, M., Goebeler, M., Knop, S., Noppeney, R., Viardot, A., Hess, G., Schuler, M., et al. (2008) · Science · doi:10.1126/science.1158545 · Cited by 1,078
Self-citationThe making of bispecific antibodies
Brinkmann, U., & Kontermann, R. E. (2017) · mAbs · doi:10.1080/19420862.2016.1268307 · Cited by 961
Topp, M. S., Kufer, P., Gökbuget, N., Goebeler, M., Klinger, M., Neumann, S., Horst, H.-A., Raff, T., Viardot, A., Schmid, M., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.32.7270 · Cited by 914
Self-citationT cell-engaging therapies — BiTEs and beyond
Goebeler, M.-E., & Bargou, R. C. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0347-5 · Cited by 675
Antibody Structure and Function: The Basis for Engineering Therapeutics
Chiu, M. L., Goulet, D. R., Teplyakov, A., & Gilliland, G. L. (2019) · Antibodies · doi:10.3390/antib8040055 · Cited by 711
Metadata
- Authors
- Mack, M., Riethmüller, G., & Kufer, P.
- Affiliations
- Institut für Immunologie (DE)
- ORCID
- Mack, M
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1995-07-18
- Volume
- 92
- Issue
- 15
- Pages
- 7021-7025
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC41463
- OpenAlex
- W2086146164
- Cited by
- 351
- References
- 39
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 15 · 2023: 7 · 2022: 10 · 2021: 20 · 2020: 12 · 2019: 22 · 2018: 19 · 2017: 20 · 2016: 12 · 2015: 22 · 2014: 16 · 2013: 13 · 2012: 14
- FWCI
- 12.32
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- bispecific antibodies, single-chain antibody, single-chain Fv fragments, CD3 antigen, colorectal cancer, minimal residual disease, tumor cell killing, CHO cell expression, Ni-NTA affinity purification, antibody therapy
- MeSH terms
- Amino Acid Sequence, Antibody Specificity, Antineoplastic Agents, Base Sequence, Cloning, Molecular, Escherichia coli, Immunoglobulin Fragments, Immunoglobulin Variable Region, Molecular Sequence Data, Recombinant Proteins, Tumor Cells, Cultured, Blotting, Western
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