Cited by 351Monoclonal and Polyclonal Antibodies ResearchToxin Mechanisms and ImmunotoxinsProtein purification and stability

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A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity.

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Mack, M, Riethmüller, G, Kufer, P·1995·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.92.15.7021PMC PMC41463

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Abstract

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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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
DOI: 10.1073/pnas.92.15.7021
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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A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity.

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