A bispecific IgG format containing four independent antigen binding sites
(2020) In Scientific Reports 10(1).- Abstract
Bispecific antibodies come in many different formats, including the particularly interesting two-in-one antibodies, where one conventional IgG binds two different antigens. The IgG format allows these antibodies to mediate Fc-related functionality, and their wild-type structure ensures low immunogenicity and enables standard methods to be used for development. It is however difficult, time-consuming and costly to generate two-in-one antibodies. Herein we demonstrate a new approach to create a similar type of antibody by combining two different variable heavy (VH) domains in each Fab arm of an IgG, a tetra-VH IgG format. The VHs are used as building blocks, where one VH is placed at its usual position, and the second VH replaces the... (More)
Bispecific antibodies come in many different formats, including the particularly interesting two-in-one antibodies, where one conventional IgG binds two different antigens. The IgG format allows these antibodies to mediate Fc-related functionality, and their wild-type structure ensures low immunogenicity and enables standard methods to be used for development. It is however difficult, time-consuming and costly to generate two-in-one antibodies. Herein we demonstrate a new approach to create a similar type of antibody by combining two different variable heavy (VH) domains in each Fab arm of an IgG, a tetra-VH IgG format. The VHs are used as building blocks, where one VH is placed at its usual position, and the second VH replaces the variable light (VL) domain in a conventional IgG. VH domains, binding several different types of antigens, were discovered and could be rearranged in any combination, offering a convenient "plug and play" format. The tetra-VH IgGs were found to be functionally tetravalent, binding two antigens on each arm of the IgG molecule simultaneously. This offers a new strategy to also create monospecific, tetravalent IgGs that, depending on antigen architecture and mode-of-action, may have enhanced efficacy compared to traditional bivalent antibodies.
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- author
- Ljungars, Anne LU ; Schiött, Torbjörn LU ; Mattson, Ulrika ; Steppa, Jessica ; Hambe, Björn ; Semmrich, Monika LU ; Ohlin, Mats LU ; Tornberg, Ulla Carin and Mattsson, Mikael
- organization
- publishing date
- 2020-01-31
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 10
- issue
- 1
- article number
- 1546
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85078856098
- pmid:32005942
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-020-58150-z
- language
- English
- LU publication?
- yes
- id
- cfa11269-2ee5-4f72-9e98-c6dd0b83725d
- date added to LUP
- 2020-02-11 15:45:37
- date last changed
- 2024-09-04 17:42:01
@article{cfa11269-2ee5-4f72-9e98-c6dd0b83725d, abstract = {{<p>Bispecific antibodies come in many different formats, including the particularly interesting two-in-one antibodies, where one conventional IgG binds two different antigens. The IgG format allows these antibodies to mediate Fc-related functionality, and their wild-type structure ensures low immunogenicity and enables standard methods to be used for development. It is however difficult, time-consuming and costly to generate two-in-one antibodies. Herein we demonstrate a new approach to create a similar type of antibody by combining two different variable heavy (VH) domains in each Fab arm of an IgG, a tetra-VH IgG format. The VHs are used as building blocks, where one VH is placed at its usual position, and the second VH replaces the variable light (VL) domain in a conventional IgG. VH domains, binding several different types of antigens, were discovered and could be rearranged in any combination, offering a convenient "plug and play" format. The tetra-VH IgGs were found to be functionally tetravalent, binding two antigens on each arm of the IgG molecule simultaneously. This offers a new strategy to also create monospecific, tetravalent IgGs that, depending on antigen architecture and mode-of-action, may have enhanced efficacy compared to traditional bivalent antibodies.</p>}}, author = {{Ljungars, Anne and Schiött, Torbjörn and Mattson, Ulrika and Steppa, Jessica and Hambe, Björn and Semmrich, Monika and Ohlin, Mats and Tornberg, Ulla Carin and Mattsson, Mikael}}, issn = {{2045-2322}}, language = {{eng}}, month = {{01}}, number = {{1}}, publisher = {{Nature Publishing Group}}, series = {{Scientific Reports}}, title = {{A bispecific IgG format containing four independent antigen binding sites}}, url = {{http://dx.doi.org/10.1038/s41598-020-58150-z}}, doi = {{10.1038/s41598-020-58150-z}}, volume = {{10}}, year = {{2020}}, }