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:CD19/CD22 bispecific chimeric antigen receptor‑NK‑92 cells are developed and evaluated.
这些结果证明了抗CD19/CD22双特异性CAR-NK细胞的潜力,并表明优化NK细胞中的CAR结构可以提高CAR治疗的疗效。
抗CD19嵌合抗原受体(CAR)-T细胞已改善B细胞白血病和淋巴瘤患者的结局。然而,其应用和阳性结局仍然有限。CAR-T细胞目前受限于以自体血液作为其来源,并且其使用可导致CD19表达下调以及移植物抗宿主病和细胞因子释放综合征等并发症。本研究旨在使用来自鸡的抗CD22单克隆抗体克隆开发抗CD19/CD22双特异性CAR结构,并在自然杀伤(NK)-92细胞(一种人NK细胞系)中于体外和体内进行分析。通过靶细胞的存活评估抗CD19/CD22 CAR-NK-92细胞的细胞毒性,并使用流式细胞术计数。与其他CAR结构相比,抗CD22/CD19和环状结构的抗CD19/CD22双特异性CAR-NK-92细胞对OCI-Ly7细胞(一种人B细胞淋巴瘤细胞系)显示出改善的疗效。这些结果证明了抗CD19/CD22双特异性CAR-NK细胞的潜力,并表明优化NK细胞中的CAR结构可提高CAR治疗的疗效。
Anti-CD19 chimeric antigen receptor (CAR)-T cells have improved the outcomes of patients with B cell leukemia and lymphoma. However, their applications and positive outcomes remain limited. CAR-T cells are currently restricted to autologous blood as their source and their use can lead to downregulation of CD19 expression along with complications such as graft-versus-host disease and cytokine release syndrome. The present study aimed to develop anti-CD19/CD22 bispecific CAR structures using an anti-CD22 monoclonal antibody clone from chickens and analyze them in natural killer (NK)-92 cells, a human NK cell line, in vitro and in vivo . Anti-CD19/CD22 CAR-NK-92 cell cytotoxicity was assessed by the survival of target cells and counted using flow cytometry. Anti-CD22/CD19 and loop-structured anti-CD19/CD22 bi-specific CAR-NK-92 cells showed improved efficacy against OCI-Ly7 cells, a human B cell lymphoma cell line, compared with other CAR structures. These results demonstrate the potential of anti-CD19/CD22 bispecific CAR-NK cells and suggested that optimizing CAR structures in NK cells can improve the efficacy of CAR therapy.
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