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在儿科急性淋巴细胞白血病中表达和治疗具有双特异性T细胞参与者的ROR1+细胞

Paraskevi Diamanti¹, Bethan K Bailey², Obinna E Iheanacho²

¹NHS Blood and Transplant, Bristol, United Kingdom.

|April 16, 2025

概括

受体氨酸样孤儿受体1 (ROR1) 在急性淋巴细胞白血病 (ALL) 中过度表达,其向ROR1双特异性T细胞参与者显示出希望. 这些新疗法在临床前模型中有效降低了白血病负担,这表明了耐火性ALL的新治疗途径.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
血液学血液学血液学

背景情况:

受体氨酸样孤儿受体1 (ROR1) 在血液癌症中过度表达,包括急性淋巴细胞白血病 (ALL),在正常组织中表达有限.
在B细胞前体 (BCP) ALL和T细胞ALL (T-ALL) 中,ROR1被发现在白血病传播细胞 (LPC) 上,这些ROR1阳性细胞可以在标准诱导治疗中存活下来.

研究的目的:

调查儿童BCP-ALL和T-ALL中准ROR1的治疗潜力.
在临床前ALL模型中评估ROR1双特异性T细胞诱导剂 (Teng) 的疗效.

主要方法:

在初级BCP-ALL和T-ALL细胞上量化ROR1表达和抗原密度.
在体外使用原始ALL细胞和T细胞评估ROR1Teng的疗效.
在体内有效性研究使用免疫缺陷小鼠移植初级ALL并用ROR1Teng治疗.

主要成果:

与BCP-ALL相比,T-ALL的ROR1表达显著更高,CD34-/CD19+ (BCP-ALL) 和CD34-/CD7+ (T-ALL) LPC的水平最高.
在体外,ROR1 Teng与单独的T细胞相比,在BCP和T-ALL中显著降低了ALL细胞存活率.
在体内,ROR1 Teng治疗导致BCP-ALL和T-ALL模型中的白血病负担大幅降低,显示出强大的抗白血病活性.

结论:

在ALL中,ROR1是一个有前途的治疗标,特别是在抵抗当前治疗的ROR1+白血病传播细胞中.
ROR1 Teng在临床前模型中显示出显著的抗白血病活性,并可能代表耐火性BCP-ALL的可行治疗选择.

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