Academic Journal
A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity
| Title: | A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity |
|---|---|
| Authors: | Aruto Sugiyama, Mitsuo Umetsu, Hikaru Nakazawa, Teppei Niide, Tomoko Onodera, Katsuhiro Hosokawa, Shuhei Hattori, Ryutaro Asano, Izumi Kumagai |
| Source: | Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
| Publisher Information: | Nature Portfolio, 2017. |
| Publication Year: | 2017 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Medicine, Science |
| More Details: | Abstract Small bispecific antibodies that induce T-cell–mediated cytotoxicity have the potential to damage late-stage tumor masses to a clinically relevant degree, but their cytotoxicity is critically dependent on their structural and functional properties. Here, we constructed an optimized procedure for identifying highly cytotoxic antibodies from a variety of the T-cell–recruiting antibodies engineered from a series of antibodies against cancer antigens of epidermal growth factor receptor family and T-cell receptors. By developing and applying a set of rapid operations for expression vector construction and protein preparation, we screened the cytotoxicity of 104 small antibodies with diabody format and identified some with 103-times higher cytotoxicity than that of previously reported active diabody. The results demonstrate that cytotoxicity is enhanced by synergistic effects between the target, epitope, binding affinity, and the order of heavy-chain and light-chain variable domains. We demonstrate the importance of screening to determine the critical rules for highly cytotoxic antibodies. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-017-03101-4 |
| Access URL: | https://doaj.org/article/f18cb9ec074743a0b52efdd168550715 |
| Accession Number: | edsdoj.f18cb9ec074743a0b52efdd168550715 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 20452322 |
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| DOI: | 10.1038/s41598-017-03101-4 |
| Published in: | Scientific Reports |
| Language: | English |