重定向人抗生物素蛋白修饰的CAR-T细胞过继免疫治疗表达EGF... - 中国病毒学论坛|我们一直在坚持！

There has been significant progress in the design of chimeric antigen receptors (CAR) for adoptive immunotherapy targeting tumor-associated antigens. However, the challenge of monitoring the therapy in real time has been continually ignored. To address this issue, we developed optical molecular imaging approaches to evaluate a recently reported novel CAR strategy for adoptive immunotherapy against glioma xenografts expressing EGFRvIII. We initially biotinylated a novel anti-EGFRvIII monoclonal antibody (biotin-4G1) to pre-target EGFRvIII+ gliomas and then redirect activated avidin-CAR expressing T cells against the pre-targeted biotin-4G1. By optical imaging study and bio-distribution analysis, we confirmed the specificity of pre-target and target and determined the optimal time for T cells adoptive transfer in vivo. The results showed this therapeutic strategy offered efficient therapy effect to EGFRvIII+ glioma-bearing mice and implied that optical imaging is a highly useful tool in aiding in the instruction of clinical CAR-T cells adoptive transfer in future.

摘要: 嵌合抗原受体（CAR）用于肿瘤相关抗原免疫治疗的设计已经取得了显著的进展。然而，一直忽视了实时监测治疗这一方面的挑战。为了解决这个问题，我们开发了一种光学分子成像来评估一个最近报道的新CAR-T治疗方案——过继免疫治疗表达EGFRvIII的胶质瘤。我们最初装备了一种新型的抗EGFR单克隆抗体（biotin-4g1），预靶向EGFRvIII 阳性的胶质瘤，然后用重定向活化的人抗生素蛋白修饰的CAR-T细胞来对抗预先靶向的生物素-4G1。通过光学成像研究和生物分布分析，证实了预靶和靶点的特异性，并确定了T细胞在体内过继治疗的最佳时机。结果表明这个治疗策略在EGFRvIII阳性的胶质瘤小鼠体内有良好的效果，也预示了光学成像是协助临床CAR-T细胞过继移植在未来教学中的一个非常有用的工具。