结果显示，在人源化小鼠模型和非人灵长类动物中，经过 AERA-109 治疗后， 血液和组织中的 B 细胞被 深度耗竭。Aera 公司计划在 2026 年年中推进 AERA-109 进入临床开发阶段。 AERA-109 利用专有的 靶向脂质纳米颗粒 （tLNP） 递送平台和 CAR-T 技术，直接在体内靶向重编程 CD8 + T 细胞，为严重自身免疫疾病提供了一种潜在疗法，具有更高的精准度和更好的安全性。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 2025 年 9 月 24 日，在 第十届 CAR-TCR 峰会上， Aera Therapeutics 展示了其候选疗法 AERA-109 的临床前数据，这是一款 in vivo CAR-T 细胞疗法 ，旨在治疗多种 B 细胞介导的自身免疫疾病 （例如系 统性红斑狼疮） 。 Aera Therapeutics 由 CRISPR 基因编辑先驱 张锋 教授等人创立，该公司于 2023 年宣布完成 1.93 亿美 元融资并正式亮相 。 创始团队还包括 RNAi 疗法巨 头 Alnylam 公司前高管 Akin Akinc 和前创始 CEO John Maraganore 。 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 2021 年 8 月，德国埃尔朗根-纽伦堡大学 Georg Schett 教授团队 研究人员在《 新英格兰医学杂志 》 （NEJM） 发表论文 【1】 ，首次使用 CAR-T 细胞疗法 来治疗 系统性红斑狼疮 ，帮助患者得到了快速且持久缓解。 此后，研究人员利用 CAR-T 细胞疗法成功治疗了多种自身免疫疾病。然而，传统的 CAR-T 细胞疗法流程复杂、成本高昂，且患者在治疗前需要进行化疗清髓预 处理，这可能带来严重副作用。 2025 年 9 月 17 日，在 《 新英格兰医学杂志 》 （NEJM） 发表了题为： In Vivo CD19 CAR T-Cell Therapy for Refractory Systemic Lupus Erythematosus 的论文 【2】 。 这是 全球首次基于 mRNA-LNP 的 in vivo CAR-T 细胞疗法进行的人体临床研究 ，研究团队利用 脂质纳米颗粒 （LNP） 将 CD19 CAR mRNA 直接递送至 CD8 + T 细胞，从而在体内原位生成具有功能活性的 CAR-T 细胞。 该论文展示了对 5 例难治性 系 ...

Core Viewpoint - The article discusses the promising efficacy of CAR-T cell therapy in treating relapsed or refractory multiple myeloma, highlighting the transition from traditional autologous CAR-T to in vivo CAR-T approaches, which simplify the manufacturing process and reduce costs [2][3][4]. Group 1: In Vivo CAR-T Therapy - In vivo CAR-T therapy involves directly delivering CAR transgenes to endogenous T cells within the body, eliminating the need for complex manufacturing and storage processes associated with traditional CAR-T therapies [3][4]. - A clinical study published in The Lancet reported the first human trial data for in vivo CAR-T therapy targeting B-cell maturation antigen (BCMA) in multiple myeloma patients, demonstrating effective treatment in four patients [4][18]. Group 2: ESO-T01 Development - ESO-T01 is a novel lentiviral vector designed for in vivo T cell engineering, developed by EsoBiotec and Prigen, featuring a humanized single-domain antibody CAR targeting BCMA [6][9]. - The vector has been engineered to reduce immunogenicity and enhance specificity, including mutations to the VSVG protein and overexpression of CD47 to evade the immune system [6]. Group 3: Clinical Trial Results - The ongoing Phase 1 trial involved four adult patients with relapsed or refractory multiple myeloma, all of whom had previously shown disease progression despite multiple treatments [9][10]. - Initial dosing of ESO-T01 was set at 2.0×10^8 transduction units, with all patients experiencing acute inflammatory responses post-infusion, including fever and low blood pressure [11][13]. - By the end of the two-month follow-up, two patients achieved stringent complete responses, while the other two showed partial responses with tumor shrinkage [12][14]. Group 4: Safety and Efficacy Observations - The trial noted significant hematological toxicities, including neutropenia and thrombocytopenia, but most adverse effects resolved during follow-up [13]. - The presence of CAR-T cells was first detected in peripheral blood between days 4-8 post-infusion, peaking between days 10-17, indicating effective T cell expansion [14][18]. - The study provides valuable data for future research on in vivo CAR-T therapies, emphasizing the potential of ESO-T01 in treating difficult-to-manage multiple myeloma cases [19].