决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Multivalent aptamer engineered and functionalized NK cells for enhanced adoptive immunotherapy in CD30-positive malignant lymphoma.
过继性细胞疗法是治疗多种血液系统恶性肿瘤的一项显著成就。
过继性细胞疗法是治疗多种血液系统恶性肿瘤的一项显著成就。在这些基于细胞的疗法中,嵌合抗原受体自然杀伤(CAR-NK)细胞受到越来越多的关注,因为与 CAR-T 细胞不同,它们与细胞因子释放综合征、免疫效应细胞相关神经毒性综合征或移植物抗宿主病的风险无关。CAR-NK 细胞具有增强的靶向特性,并已证明对多种类型的癌症具有治疗效力。然而,它们面临重大挑战,包括操作程序复杂、长期使用相关的高成本以及安全性问题。适配体是单链寡核苷酸,因其对靶标具有高度特异性结合能力而被称为“化学抗体”。在本研究中,我们设计了一种含四条 CD30 适配体链的多价适配体寡核苷酸复合物,利用点击化学对 NK 细胞进行工程化改造和功能化。在适配体引导下,多价适配体寡核苷酸复合物 NK 细胞特异性结合 CD30 阳性淋巴瘤细胞,并在体外和体内触发比亲本 NK 细胞更有效的抗肿瘤效应。因此,所提出的方法赋予 NK 细胞肿瘤特异性靶向能力,并增强其在 CD30 阳性淋巴瘤中的过继治疗效率,在恶性淋巴瘤的临床治疗中显示出巨大的应用潜力。
Adoptive cell therapy is a notable achievement in the treatment of various hematological malignancies. Among these cell-based therapies, chimeric antigen receptor natural killer (CAR-NK) cells have received increasing attention because, unlike CAR-T cells, they are not associated with the risk of cytokine release syndrome, immune-effector-cell-associated neurotoxicity syndrome, or graft-versus-host disease. CAR-NK cells have enhanced targeting properties and demonstrated therapeutic efficacy against various types of cancer. However, they face substantial challenges, including complex operational procedures, high cost associated with long-term use, and safety concerns. Aptamers are single-stranded oligonucleotides and known as "chemical antibodies" because of their highly specific binding ability to targets. In this study, we designed a multivalent aptamer oligonucleotide complex containing four strands of CD30 aptamers to engineer and functionalize NK cells using click chemistry. Under aptamer guidance, multivalent aptamer oligonucleotide complex NK cells specifically bind to CD30-positive lymphoma cells and trigger more effective antitumor effects than that of parental NK cells, both in vitro and in vivo . Therefore, the proposed approach endows NK cells with tumor-specific targeting ability and enhances their adoptive therapeutic efficiency in CD30-positive lymphoma, showing substantial potential for application in the clinical treatment of malignant lymphoma.
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