尼古丁胺增强了自然杀手细胞的功能,并在患有非霍奇金淋巴瘤的患者中产生缓解
Frank Cichocki1, Bin Zhang1, Cheng-Ying Wu1
1Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Science translational medicine
|July 19, 2023
概括
尼古丁胺增强了自然杀手 (NK) 细胞治疗白血病和淋巴瘤,通过改善细胞存活,功能和持久性. 一项临床试验显示,GDA-201在患有晚期非霍奇金淋巴瘤的患者中显示出有前途的结果.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞疗法细胞疗法
- 癌症研究 癌症研究
背景情况:
- 全基性自然杀手 (NK) 细胞采用转移显示出治疗复发性/耐药性白血病和淋巴瘤的前景.
- 提高NK细胞的存活和功能对于提高临床疗效至关重要.
- 介质素-15 (IL-15) 是NK细胞扩张的关键细胞因子.
研究的目的:
- 为了研究尼古丁胺胺 (NAM) 对活体扩展的NK细胞的影响.
- 在一期临床试验中评估GDA-201 (IL-15和NAM扩展NK细胞) 的安全性和有效性.
- 评估NAM对NK细胞归宿,代谢,细胞毒性和持久性的影响.
主要方法:
- 用IL-15和NAM培养了NK细胞的活体培养.
- 分析了l-选择素 (CD62L) 和分叉盒O1 (FOXO1) 的表达.
- 评估了代谢特征,细胞毒性和细胞因子的产生.
- 一个第一阶段临床试验 (NCT03019666) 评估了GDA-201与复发/耐药非霍奇金淋巴瘤 (NHL) 和多发性骨髓瘤 (MM) 患者的单克隆抗体结合.
主要成果:
- NAM培养的NK细胞显示CD62L的稳定诱导,与增强的FOXO1稳定性相关.
- NAM促进了新陈代谢变化,增加了葡萄糖的流量,并提供了对氧化应激的保护.
- 接受NAM治疗的NK细胞表现出增强的细胞毒性,炎症性细胞因子的产生,以及改善的活体内持续性.
- 在GDA-201试验中,先进的NHL患者的整体应答率为74%,有13个完整反应.
- 检测到GDA-201细胞长达14天,并保持了有利的代谢概况.
结论:
- 用IL-15和NAM扩大NK细胞的ex vivo扩张增强了它们的抗癌特性.
- GDA-201在治疗先进的NHL和MM方面显示出良好的安全性和有效性.
- 这种细胞疗法具有在癌症治疗中进一步发展的巨大潜力.
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