Department of Neurosurgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
Mol Cancer. 2023 Jan 9;22(1):3. doi: 10.1186/s12943-022-01711-9.
This study aimed to validate whether infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells is safe and whether CAR-T cells exert anti-glioblastoma (GBM) activity.
A total of eight patients with GD2-positive GBM were enrolled and infused with autologous GD2-specific 4SCAR-T cells, either through intravenous administration alone or intravenous combined with intracavitary administration.
4SCAR-T cells expanded for 1-3 weeks and persisted at a low frequency in peripheral blood. Of the eight evaluable patients, four showed a partial response for 3 to 24 months, three had progressive disease for 6 to 23 months, and one had stable disease for 4 months after infusion. For the entire cohort, the median overall survival was 10 months from the infusion. GD2 antigen loss and infiltrated T cells were observed in the tumor resected after infusion.
Both single and combined infusions of GD2-specific 4SCAR-T cells in targeting GBM were safe and well tolerated, with no severe adverse events. In addition, GD2-specific 4SCAR-T cells partially mediate antigen loss and activate immune responses in the tumor microenvironment. Validation of our findings in a larger prospective trial is warranted.
ClinicalTrials.gov Identifier: NCT03170141 . Registered 30 May 2017.
本研究旨在验证 GD2 特异性第四代安全设计嵌合抗原受体（4SCAR）-T 细胞输注是否安全，以及 CAR-T 细胞是否具有抗胶质母细胞瘤（GBM）活性。
共纳入 8 例 GD2 阳性 GBM 患者，采用静脉输注或静脉联合腔内输注的方式输注自体 GD2 特异性 4SCAR-T 细胞。
4SCAR-T 细胞在 1-3 周内扩增，并在外周血中以低频率持续存在。在 8 例可评估患者中，4 例患者在 3 至 24 个月内出现部分缓解，3 例患者在 6 至 23 个月内出现疾病进展，1 例患者在输注后 4 个月出现疾病稳定。对于整个队列，从输注开始的中位总生存期为 10 个月。输注后在肿瘤切除标本中观察到 GD2 抗原丢失和浸润 T 细胞。
GD2 特异性 4SCAR-T 细胞单独或联合靶向 GBM 的输注是安全且耐受良好的，无严重不良事件。此外，GD2 特异性 4SCAR-T 细胞部分介导抗原丢失，并激活肿瘤微环境中的免疫反应。有必要在更大的前瞻性试验中验证我们的发现。
ClinicalTrials.gov 标识符：NCT03170141。注册于 2017 年 5 月 30 日。
