肿瘤细胞治疗研究
英文原题：Intracerebroventricular bivalent CAR T cells targeting EGFR and IL-13Rα2 in recurrent glioblastoma: a phase 1 trial.
这些发现表明，脑室内递送双价 CART-EGFR-IL13R 2 是可行的，且似乎是安全的。
胶质母细胞瘤（GBM）是成人最常见的原发性脑癌，中位总生存期（OS）为12–15个月。对于一线放化疗后复发的GBM（rGBM），有效治疗仍是重大未满足的医疗需求。本文报告一项1期试验的剂量递增和探索阶段结果，该试验在EGFR扩增型rGBM患者中脑室内递送双特异性嵌合抗原受体（CAR）T细胞，靶向表皮生长因子受体（EGFR）806表位和白细胞介素13受体α2（IL-13Rα2），即CART-EGFR-IL13Rα2细胞。主要终点包括剂量限制性毒性、最大耐受剂量和扩展推荐剂量的确定，以及不良事件发生情况；次要终点包括影像学客观缓解、缓解持续时间、无进展生存期和OS。共18例患者接受CART-EGFR-IL13Rα2细胞治疗。最大耐受剂量确定为2.5×10⁷个细胞。18例患者中，10例（56%）出现3级神经毒性，无人出现4–5级神经毒性。在输注CAR-T细胞时有可测量病灶的13例患者中，8例（62%）出现肿瘤消退；其中1例依据修订版神经肿瘤反应评估标准达到确认的部分缓解（影像学客观缓解率8%；90%置信区间0–32%），另有1例患者疾病稳定持续超过16个月。中位无进展生存期为1.9个月（90%置信区间1.1–3.4个月）；数据截点时尚未达到中位OS（中位随访时间8.1个月）。这些结果表明，脑室内递送双特异性CART-EGFR-IL13Rα2具有可行性且似乎安全；该细胞具有生物活性，并在rGBM中显示抗肿瘤作用信号。ClinicalTrials.gov注册号：NCT05168423。
Glioblastoma (GBM) is the most common primary brain cancer in adults and carries a median overall survival (OS) of 12-15 months. Effective therapy for recurrent GBM (rGBM) following frontline chemoradiation is a major unmet medical need. Here we report the dose escalation and exploration phases of a phase 1 trial investigating intracerebroventricular delivery of bivalent chimeric antigen receptor (CAR) T cells targeting epidermal growth factor receptor (EGFR) epitope 806 and interleukin-13 receptor alpha 2 (IL-13R 2), or CART-EGFR-IL13R 2 cells, in patients with EGFR-amplified rGBM. Primary endpoints included dose-limiting toxicity, determination of the maximum tolerated dose and recommended dose for expansion, and occurrence of adverse events. Secondary endpoints included objective radiographic response, duration of response, progression-free survival and OS. A total of 18 patients received CART-EGFR-IL13R 2 cells. The maximum tolerated dose was determined to be 2.5 10 7 cells. Of the 18 patients, 10 (56%) experienced grade 3 neurotoxicity; none had grade 4-5 neurotoxicity. Of 13 patients, 8 (62%) with measurable disease at the time of CAR T cell infusion experienced tumor regression, with one confirmed partial response by Modified Response Assessment in Neuro-Oncology criteria (objective radiographic response, 8%; 90% confidence interval, 0-32%) and one patient with ongoing durable stable disease lasting over 16 months. Median progression-free survival was 1.9 months (90% confidence interval, 1.1-3.4 months), and median OS was not yet reached at the time of data cut-off (median follow-up time, 8.1 months). These findings indicate that intracerebroventricular delivery of bivalent CART-EGFR-IL13R 2 is feasible and appears safe. CART-EGFR-IL13R 2 cells are bioactive and exhibit a signal of antitumor effect in rGBM. ClinicalTrials.gov registration: NCT05168423 .
MEMBER ACCOUNT
登录成功会直接打开下一页。
