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针对B细胞淋巴细胞恶性瘤的新型BAFF-R CAR-T疗法的转化开发

Yan Luo¹, Yaqing Qie¹, Martha E Gadd¹

¹Regenerative Immunotherapy and CAR-T Translational Research Program, Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL, 32224, USA.

Cancer immunology, immunotherapy : CII

|October 9, 2023

概括

一种针对BAFF-R的新CAR-T疗法对治疗复发性白血病和淋巴瘤,包括慢性淋巴细胞白血病 (CLL),即使在CD19阴性病例中也是有前途的. 这种新的方法已经进入临床试验.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
细胞疗法细胞疗法

背景情况:

目前针对CD19的CAR-T疗法面临着复发性/耐药性疾病的挑战,以及在CLL等血液性恶性瘤中具有可变的疗效.
B细胞激活因子受体 (BAFF-R) 是B细胞增殖和成熟的关键调节器,具有潜在的治疗标.

研究的目的:

开发和评估一种针对BAFF-R针对血液性恶性瘤的新型化学抗原受体T细胞 (CAR-T) 疗法.
评估这种新疗法的疗效,MC10029 CAR-T细胞,针对白血病,淋巴瘤,特别是慢性淋巴细胞白血病 (CLL),包括CD19阴性疾病的模型.

主要方法:

产生了针对BAFF-R的新型单克隆抗体,并构建了MC10029 CAR结构.
在实验室和体内使用白血病 (Nalm-6) 和淋巴瘤 (Z138) 细胞系,包括CD19淘汰赛模型,评估了MC10029 CAR-T细胞细胞毒性.
对MEC-1 CLL细胞系和原发性CLL患者样本进行了有效性测试,使用了健康的捐赠者工程和自身的CAR-T细胞.

主要成果:

在临床前模型中,MC10029 CAR-T细胞对瘤细胞表现出抗原特异性细胞毒性.
该疗法对CD19阴性瘤细胞表现出强大的抗瘤作用,解决了当前治疗方法的关键局限性.
MC10029 CAR-T细胞对CLL细胞系有效,最重要的是对初级CLL受试者样本有效,证实BAFF-R是CLL中可行的标.

结论:

针对BAFF-R的MC10029CAR-T细胞治疗是一种有前途的新策略,用于血液性恶性瘤,特别是CLL.
该疗法在复发性/耐药性疾病模型和来自患者的CLL样本中显示出有效性.
成功的临床前开发已经导致IND批准进行第一阶段临床试验,这标志着重大进展.

关键词:

在B细胞恶性瘤中.这就是BAFF-R.在CART-T中,我们可以使用CAR-T.免疫治疗是一种免疫疗法.在白血病中,白血病.淋巴瘤是一种淋巴瘤.

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