肿瘤细胞治疗研究
英文原题：In vivo CAR T-cell generation in nonhuman primates using lentiviral vectors displaying a multidomain fusion ligand.
此外，在未进行淋巴细胞清除化疗的情况下，向非人灵长类动物给予 VVPs 可大量生成抗 CD20 CAR-T 细胞，并使 B 细胞完全耗竭持续 >10 周。
嵌合抗原受体（CAR）T 细胞疗法治疗 B 细胞恶性肿瘤已显示变革性疗效，但高昂成本和制造复杂性阻碍其广泛应用。为克服这些障碍，我们开发了 VivoVec 平台，这是一种可在体内生成 CAR T 细胞的慢病毒载体。本文介绍如何以多结构域融合蛋白形式，将 T 细胞活化和共刺激信号整合至 VivoVec 颗粒（VVP）表面，并证明这可增强体内转导并改善 CAR T 细胞抗肿瘤功能。此外，在未进行淋巴清除化疗的情况下，向非人灵长类动物给予 VVP，可强效生成抗 CD20 CAR T 细胞，并使 B 细胞完全清除超过 10 周。这些数据在具有转化相关性的模型中验证了 VivoVec 平台，支持其进入人体临床试验，为 CAR T 细胞疗法领域带来范式转变。
Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformative efficacy in treating B-cell malignancies. However, high costs and manufacturing complexities hinder their widespread use. To overcome these hurdles, we have developed the VivoVec platform, a lentiviral vector capable of generating CAR T cells in vivo. Here, we describe the incorporation of T-cell activation and costimulatory signals onto the surface of VivoVec particles (VVPs) in the form of a multidomain fusion protein and show enhanced in vivo transduction and improved CAR T-cell antitumor functionality. Furthermore, in the absence of lymphodepleting chemotherapy, administration of VVPs into nonhuman primates resulted in the robust generation of anti-CD20 CAR T cells and the complete depletion of B cells for >10 weeks. These data validate the VivoVec platform in a translationally relevant model and support its transition into human clinical testing, offering a paradigm shift in the field of CAR T-cell therapies.
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