Selection for Anti-transferrin Receptor Bispecific T-cell Engager in Different Molecular Formats
Selection for Anti-transferrin Receptor Bispecific T-cell Engager in Different Molecular Formats
复制标题
不同分子形式的抗转铁蛋白受体双特异性 T 细胞接合剂的选择。
DOI：
10.1007/s11596-020-2143-y
复制
发表时间：
2020-02-01
影响因子：
2.4
通讯作者：
Lei, Ping
中科院分区：
文献类型：
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作者：
Fu, Ming-peng;Guo, Zi-long;Lei, Ping
从多种结构中选择一种理想的分子形式是开发双特异性抗体（BsAb）的一项重大挑战。为了选择一种用于临床应用的抗CD3×抗转铁蛋白受体（TfR）双特异性抗体的理想形式，我们构建了两种广泛应用形式的TfR双特异性T细胞衔接器（BiTE），包括单链串联单链可变片段（scFvs）和双链双抗体，并在体外评估了它们的功能特性。结果表明，两种形式的TfR - BiTE都能有效杀伤TfR⁺的HepG2细胞。然而，与双链双抗体相比，scFvs在抗原结合和杀伤TfR⁺靶细胞方面更有效。此外，还将对scFvs中不同的结构域顺序进行评估，因为在免疫治疗策略中，单 - TfR - CD3 - His优于单 - CD3 - TfR - His。因此，单链串联TfR - CD3形式在癌症治疗中更适合进一步研究。
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 x 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.