Summary
Selecting an ideal molecular format from diverse structures is a major challenge in developing a bispecific antibody (BsAb). To choose an ideal format of anti-CD3 × anti-transferrin receptor (TfR) bispecific antibodies for clinical application, we constructed TfR bispecific T-cell engager (BiTE) in two extensively applied formats, including single-chain tandem single-chain variable fragments (scFvs) and double-chain diabodies, and evaluated their functional characterizations in vitro. Results demonstrated that TfR-BiTE in both formats directed potent killing of TfR+ HepG2 cells. However, compared to two-chain diabodies, scFvs were more efficient in antigen binding and TfR+ target killing. Furthermore, different domain orders in scFvs would also be evaluated because single-TfR-CD3-His was preferable to single-CD3-TfR-His in immunotherapeutic strategies. Thus, the single-chain tandem TfR-CD3 format was favored for further investigation in cancer therapy.
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The authors have declared that no conflict of interest exists.
This research was supported by grants from the National Natural Science Foundation of China (No. 31570937 and No. 81871391), Natural Science Foundation of Hubei Province of China (No. 2017CFB707), the Fundamental Research Funds for the Central Universities of China (No. HUST: 2018KFYYXJJ086) and Graduates’ Innovation Foundation of Huazhong University of Science and Technology (No. 5003510001).
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Fu, Mp., Guo, Zl., Tang, Hl. et al. Selection for Anti-transferrin Receptor Bispecific T-cell Engager in Different Molecular Formats. CURR MED SCI 40, 28–34 (2020). https://doi.org/10.1007/s11596-020-2143-y
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DOI: https://doi.org/10.1007/s11596-020-2143-y