mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting.
mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting.
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DOI：
10.1080/2162402x.2017.1368604
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发表时间：
2017
期刊：
影响因子：
7.2
通讯作者：
Finn OJ
中科院分区：
文献类型：
--
作者：
Lohmueller JJ;Ham JD;Kvorjak M;Finn OJ
嵌合抗原受体 T 细胞 (CAR-T) 是有前景的癌症治疗方法。然而，由于癌细胞可以失去CAR靶向抗原并避免破坏，因此有人提出用多个CAR靶向多个抗原。我们在这里展示了一种不太麻烦的替代方案，即与肿瘤靶向抗体上的标签结合的反标签 CAR (AT-CAR)。我们使用亲和力增强的单体链霉亲和素 2 (mSA2) 生物素结合结构域创建了新型 AT-CAR，该结构域在 T 细胞上表达时可以靶向涂有生物素化抗体的癌细胞。表达具有 CD28-CD3z 和 4–1BB-CD3z 信号域的 mSA2 CAR 的人 T 细胞被板固定的生物素和涂有针对肿瘤相关抗原 CD19 和 CD20 的生物素化抗体的肿瘤细胞激活。此外，mSA2 CAR T 细胞能够以抗体剂量依赖性方式介导癌细胞裂解和 IFNγ 产生。 mSA2 CAR 是一种通用 AT-CAR，可以与生物素化的肿瘤特异性抗体结合，潜在地针对许多不同的肿瘤类型。
Chimeric antigen receptor T cells (CAR-Ts) are promising cancer therapeutics. However, since cancer cells can lose the CAR-targeted antigen and avoid destruction, targeting multiple antigens with multiple CARs has been proposed. We illustrate here a less cumbersome alternative, anti-tag CARs (AT-CARs) that bind to tags on tumor-targeting antibodies. We have created novel AT-CARs, using the affinity-enhanced monomeric streptavidin 2 (mSA2) biotin-binding domain that when expressed on T cells can target cancer cells coated with biotinylated antibodies. Human T cells expressing mSA2 CARs with CD28-CD3ζ and 4–1BB-CD3ζ signaling domains were activated by plate-immobilized biotin and by tumor cells coated with biotinylated antibodies against the tumor-associated antigens CD19 and CD20. Furthermore, mSA2 CAR T cells were capable of mediating cancer cell lysis and IFNγ production in an antibody dose-dependent manner. The mSA2 CAR is a universal AT-CAR that can be combined with biotinylated tumor-specific antibodies to potentially target many different tumor types.