The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
"Diabodies": small bivalent and bispecific antibody fragments.
Open accessAbstract
Bivalent and bispecific antibodies and their fragments have immense potential for practical application. Here we describe the design of small antibody fragments with two antigen-binding sites. The fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (VL) on the same polypeptide chain (VH-VL). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. As indicated by a computer graphic model of the dimers, the two pairs of domains can pack together with the antigen-binding sites pointing in opposite directions. The dimeric antibody fragments, or "diabodies," can be designed for bivalent or bispecific interactions. Starting from the monoclonal antibodies NQ11.7.22 (NQ11) and D1.3 directed against the hapten phenyloxazolone and hen egg lysozyme, respectively, we built bivalent fragments (VHNQ11-VLNQ11)2 and (VHD1.3-VLD1.3)2 and bispecific fragments VHNQ11-VLD1.3 and VHD1.3-VLNQ11. The fragments were expressed by secretion from bacteria and shown to bind specifically to the hapten and/or antigen. Those with 5- and 15-residue linkers had similar binding affinities to the parent antibodies, but a fragment with the VH domain joined directly to the VL domain was found to have slower dissociation kinetics and an improved affinity for hapten. Diabodies offer a ready means of constructing small bivalent and bispecific antibody fragments in bacteria.
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Cites
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Cited by
Making antibodies by phage display technology
Winter, G., Griffiths, A. D., Hawkins, R. E., & Hoogenboom, H. R. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.002245 · Cited by 1,573
Self-citationTherapeutic antibodies: successes, limitations and hopes for the future
Chames, P., Van Regenmortel, M., Weiss, E., & Baty, D. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00190.x · Cited by 1,382
Bispecific antibodies: a mechanistic review of the pipeline
Labrijn, A. F., Janmaat, M. L., Reichert, J. M., & Parren, P. W. H. I. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0028-1 · Cited by 1,303
Antibody arrays for high-throughput screening of antibody–antigen interactions
de Wildt, R. M. T., Mundy, C. R., Gorick, B. D., & Tomlinson, I. M. (2000) · Nature Biotechnology · doi:10.1038/79494 · Cited by 624
Stability engineering of antibody single-chain Fv fragments
Wörn, A., & Plückthun, A. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4265 · Cited by 616
Metadata
- Authors
- Holliger, P., Prospero, T., & Winter, G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1993-07-15
- Volume
- 90
- Issue
- 14
- Pages
- 6444-6448
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1996820981
- Cited by
- 874
- References
- 32
- FWCI
- 25.35
- Type
- journal article
- Language
- en
- Open access
- green
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