不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD19 嵌合抗原受体工程化 NK 细胞中 CCR7 的表达增强其向表达 CCL19 的淋巴瘤细胞迁移并提高人淋巴瘤小鼠的肿瘤控制
英文原题：CCR7 expression in CD19 chimeric antigen receptor-engineered natural killer cells improves migration toward CCL19-expressing lymphoma cells and increases tumor control in mice with human lymphoma.
查看英文原题
CCR7 expression in CD19 chimeric antigen receptor-engineered natural killer cells improves migration toward CCL19-expressing lymphoma cells and increases tumor control in mice with human lymphoma.
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研究概要
现货型 t-haNK 细胞表达 CC7 受体在体外和体内均改善其向淋巴结趋化因子的归巢，从而实现更优的肿瘤控制。
研究思路结论见上方概要
背景
嵌合抗原受体（CAR）T细胞治疗可能伴随显著毒性。经CAR工程改造的自然杀伤（NK）细胞在保持抗肿瘤效应的同时提供了更安全的替代方案。活化NK（aNK）细胞是一种从NK-92细胞系获得的临床级细胞产品，在1期试验中已证明对多种癌症具有安全性和强效细胞毒性。表达高亲和力Fc受体（haNK）或共表达CAR（t-haNK）的aNK细胞基因工程变体目前正处于1/2期临床试验中。细胞免疫疗法疗效的一个关键因素是生物分布和肿瘤浸润，这影响局部效应细胞与靶细胞比例。趋化因子CCL19和CCL21可驱动表达CCR7受体的免疫细胞募集至次级淋巴器官。
方法
由于NK-92细胞不自发表达CCR7，临床级aNK细胞被转染了含有CCR7受体、抗CD19 CAR和高亲和力CD16 Fc受体的非病毒载体。
结果
CCR7工程化CD19 t-haNK在体外对工程化分泌CCL19的K562细胞表现出显著的迁移。这一观察结果在NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG)小鼠模型中得到证实，在该模型中，表达CCL19的K562细胞皮下肿瘤显示出比CCR7阴性CD19 t-haNK细胞更高数量的浸润性CCR7_CD19 t-haNK细胞。在静脉或皮下接种分泌CCL19的Raji细胞的NSG小鼠中，与CD19 t-haNK或溶媒相比，CCR7_CD19 t-haNK治疗改善了生存和肿瘤控制。
展开英文摘要原文
METHODS
Since NK-92 cells do not spontaneously express CCR7, clinical-grade aNK cells were transfected with a non-viral vector containing the CCR7 receptor, an anti-CD19 CAR and a high-affinity CD16 Fc receptor.
RESULTS
CCR7-engineered CD19 t-haNK showed significant migration in vitro toward K562 cells engineered to secrete CCL19. This observation was confirmed in a NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG) mouse model in which subcutaneous tumors of CCL19-expressing K562 cells displayed a higher number of infiltrating CCR7_CD19 t-haNK cells than CCR7-negative CD19 t-haNK cells. In NSG mice inoculated either intravenously or subcutaneously with CCL19-secreting Raji cells, treatment with CCR7_CD19 t-haNK improved survival and tumor control compared with CD19 t-haNK or vehicle.
CONCLUSIONS
Expression of CCR7 receptor by off-the-shelf t-haNK cells improves their homing toward lymph node chemokines both in vitro and in vivo, resulting in superior tumor control.
论文信息
- 作者
- Schomer NT、Jiang ZK、Lloyd MI、Klingemann H、Boissel L
- 第一作者单位
- ImmunityBio, Inc, Culver City, California, USA.United States
- 通讯作者单位
- ImmunityBio, Inc, Culver City, California, USA. Electronic address: laurent.boissel@immunitybio.com.United States
- 文献类型
- 非美国政府资助研究
- 期刊
- Cytotherapy2022 Aug
- 原文标识
- PubMed 35400595 · DOI 10.1016/j.jcyt.2022.02.006