Huang, Shuyu and Segues, Aina and Waterfall, Martin and Wright, David and Vayssiere, Charlotte and van Duijnhoven, Sander M. J. and van Elsas, Andrea and Sijts, Alice J. A. M. and Zaiss, Dietmar M. (2022) Shortened Hinge Design of Fab x sdAb-Fc Bispecific Antibodies Enhances Redirected T-Cell Killing of Tumor Cells. BIOMOLECULES, 12 (10): 1331. ISSN , 2218-273X
Full text not available from this repository. (Request a copy)Abstract
T cell engager (TCE) antibodies have emerged as promising cancer therapeutics that link cytotoxic T-cells to tumor cells by simultaneously binding to CD3E on T-cells and to a tumor-associated antigen (TAA) expressed by tumor cells. We previously reported a novel bispecific format, the IgG-like Fab x sdAb-Fc (also known as half-IG_VH-h-CH2-CH3), combining a conventional antigen-binding fragment (Fab) with a single domain antibody (sdAb). Here, we evaluated this Fab x sdAb-Fc format as a T-cell redirecting bispecific antibody (TbsAbs) by targeting mEGFR on tumor cells and mCD3E on T cells. We focused our attention specifically on the hinge design of the sdAb arm of the bispecific antibody. Our data show that a TbsAb with a shorter hinge of 23 amino acids (TbsAb.short) showed a significantly better T cell redirected tumor cell elimination than the TbsAb with a longer, classical antibody hinge of 39 amino acids (TbsAb.long). Moreover, the TbsAb.short form mediated better T cell-tumor cell aggregation and increased CD69 and CD25 expression levels on T cells more than the TbsAb.long form. Taken together, our results indicate that already minor changes in the hinge design of TbsAbs can have significant impact on the anti-tumor activity of TbsAbs and may provide a new means to improve their potency.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DIABODY; FORMAT; bispecific antibody; cancer immunotherapy; mCD3E; mEGFR; hinge |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Jan 2024 08:07 |
| Last Modified: | 29 Jan 2024 14:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57085 |
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