ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806.
Forevertek Biotechnology Co.,Ltd, Building M0, Oversea Graduate Park National High-tech Industrial Zone, 410003, Changsha, China.
Front Biosci (Landmark Ed). 2020 Jan 1;25(2):270-282. doi: 10.2741/4806.
Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated clinical success in treatment of B-cell hematologic cancers. In this study, we compared human Transferrin epitope tagged CAR-T cells with non-tagged CAR-T cells for cytotoxicity, IFN-gamma secretion and tumor clearance in NSG mice. CD19-TF-CAR-T cells had similar cytotoxicity to CD19-CAR-T cells against cells expressing CD19 antigen: exogenously CD19 Hela cells and endogenously CD19 Raji cells. In addition, CD22-TF CAR-T cells were similarly cytotoxic against CD22 CHO cells and CD22 Raji cells. Both CD19-TF or CD22-TF-CAR-T cells secreted less IFN-gamma as compared to non-tagged CAR-T cells. In a Raji xenograft NSG mouse model, CD19-TF-CAR-T cells were as effective as CD19-CAR-T cells in reducing tumor growth and extending mouse survival. The results show that CD19-TF-CAR-T cells can be monitored using TF antibody and , and that these cells effectively killed Raji cells and with reduced secretion of IFN-gamma. Thus, these TF-tagged CAR-T cells might have improved safety and provide a basis for future clinical studies.
嵌合抗原受体 (CAR) T 细胞免疫疗法在治疗 B 细胞血液系统恶性肿瘤方面已取得临床成功。在这项研究中，我们比较了人转铁蛋白表位标记的 CAR-T 细胞与非标记的 CAR-T 细胞对 NSG 小鼠中细胞毒性、IFN-γ分泌和肿瘤清除的作用。CD19-TF-CAR-T 细胞对表达 CD19 抗原的细胞（外源性 CD19 Hela 细胞和内源性 CD19 Raji 细胞）的细胞毒性与 CD19-CAR-T 细胞相似。此外，CD22-TF CAR-T 细胞对 CD22 CHO 细胞和 CD22 Raji 细胞也具有相似的细胞毒性。与非标记的 CAR-T 细胞相比，CD19-TF 或 CD22-TF-CAR-T 细胞分泌的 IFN-γ 较少。在 Raji 异种移植 NSG 小鼠模型中，CD19-TF-CAR-T 细胞在减少肿瘤生长和延长小鼠存活方面与 CD19-CAR-T 细胞一样有效。结果表明，CD19-TF-CAR-T 细胞可以使用 TF 抗体进行监测，并且这些细胞可以有效杀伤 Raji 细胞，并减少 IFN-γ 的分泌。因此，这些 TF 标记的 CAR-T 细胞可能具有更好的安全性，并为未来的临床研究提供了基础。
