在耐火固体瘤中针对美索林的T细胞受体融合构造细胞疗法:1/2期试验临时结果
Raffit Hassan1, Marcus Butler2, Roisin E O'Cearbhaill3
1Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. hassanr@mail.nih.gov.
Nature medicine
|July 27, 2023
概括
加沃卡巴丁基自身细胞 (gavo-cel) 是一种新的T细胞受体融合结构,在表达美索林的固体瘤中显示出有前途的抗瘤活性. 需要进一步研究,但由于潜在的狭窄治疗窗口,需要仔细监测.
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:
- 梅索特林是一种与瘤相关的抗原,在各种固体瘤中过度表达.
- 治疗不耐用的固体瘤存在重大未满足的医疗需求.
- 目前正在研究针对美索林的新型治疗策略.
研究的目的:
- 在表达美索林的固体瘤患者中评估gavocabtagene autoleucel (gavo-cel) 的安全性和耐受性.
- 确定获取细胞的推第二阶段剂量 (RP2D).
- 评估收获细胞的初步疗效.
主要方法:
- 第1阶段的结果来自正在进行的第1/2阶段的收获细胞试验.
- 患者在升级剂量中接受了dowa-cel,有或没有淋巴细胞减少 (LD).
- 安全终点包括剂量限制性毒性 (DLT),肺炎和细胞因子释放综合征 (CRS). 疗效终点包括整体反应率 (ORR) 和整体存活率 (OS).
主要成果:
- 在LD之后,RP2D被确定为1x10^8细胞/m^2.
- DLT包括3级肺炎和5级支气管支气管出血.
- 在RP2D时,没有观察到3级+肺炎;15%的患者出现了3级+CRS.
- 在可评估患者中,ORR为20% (13%确诊),6个月的OS率为70%.
结论:
- 在治疗不耐药的表达美索林的固体瘤患者中,Gavo-cel表现出令人鼓舞的抗瘤活性.
- 治疗可能有一个狭窄的治疗窗口,需要仔细监测安全性.
- 在这种患者群体中,Gavo-cel需要进一步研究.
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