CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
靶向 B 细胞和长寿命浆细胞的免疫治疗有效清除预存的供者特异性同种抗体
英文原题：Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies.
查看英文原题
Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies.
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中文摘要
既存抗人白细胞抗原（HLA）同种异体抗体是移植的一大障碍。当前脱敏方法无法有效清除同种异体抗原特异性记忆B细胞（Bmem）和长寿命浆细胞（LLPC），因此效果不佳。
我们在皮肤预致敏小鼠胰岛同种异体移植模型中，评估靶向CD19和B细胞成熟抗原（BCMA）的嵌合抗原受体（CAR）T细胞清除同种异体抗体的效果。
研究发现，在已致敏宿主中，靶向Bmem和LLPC的CAR-T 细胞可清除供者特异性同种异体抗体（DSA），并减轻后续胰岛同种异体移植物的超急性排斥。随后，我们评估了CAR-T 脱敏疗法在多发性骨髓瘤（MM）患者中的临床效果；这些患者存在既存HLA同种异体抗体，并接受CART-BCMA与CART-19联合治疗（ClinicalTrials.gov：NCT03549442）。观察到具有临床意义的同种异体抗体降低。这些发现为在高度致敏候选者中开展CAR-T 免疫疗法的临床评估提供了合理依据，以促进移植成功。
展开英文摘要原文
Pre-existing anti-human leukocyte antigen (HLA) allo-antibodies constitute a major barrier to transplantation. Current desensitization approaches fail due to ineffective depletion of allo-specific memory B cells (Bmems) and long-lived plasma cells (LLPCs).
We evaluate the efficacy of chimeric antigen receptor (CAR) T cells targeting CD19 and B cell maturation antigen (BCMA) to eliminate allo-antibodies in a skin pre-sensitized murine model of islet allo-transplantation.
We find that treatment of allo-sensitized hosts with CAR T cells targeting Bmems and LLPCs eliminates donor-specific allo-antibodies (DSAs) and mitigates hyperacute rejection of subsequent islet allografts.
We then assess the clinical efficacy of the CAR T therapy for desensitization in patients with multiple myeloma (MM) with pre-existing HLA allo-antibodies who were treated with the combination of CART-BCMA and CART-19 (ClinicalTrials. gov: NCT03549442) and observe clinically meaningful allo-antibody reduction.
These findings provide logical rationale for clinical evaluation of CAR T-based immunotherapy in highly sensitized candidates to promote successful transplantation.
论文信息
- 作者
- Zhang Z、Markmann C、Yu M、Agarwal D、Rostami S、Wang W、Liu C、Zhao H
- 第一作者单位
- Department of Pathology & Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.United States
- 通讯作者单位
- Department of Pathology & Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: vbhoj@pennmedicine.upenn.edu.United States
- 文献类型
- 非美国政府资助研究 · 美国 NIH 资助研究
- 期刊
- Cell reports. Medicine2023 Dec 19
- 原文标识
- PubMed 38118406 · DOI 10.1016/j.xcrm.2023.101336
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