Table 4.
Clinical study outcomes of CAR-T cell therapy for gliomas
| Disease type | Target | Registration Number | Research Phase | Partici-pants | Time | Research Institution | Authors | Clinical outcomes | Adverse events |
|---|---|---|---|---|---|---|---|---|---|
| GBM | EGFRvIII | NCT02209376 | phase 1 | 10 | 2017 | Perelman School of Medicine at the University of Pennsylvania, USA | O’Rourke DM, et al [44] | Median OS: 8 months |
CRS:0; ICANS:30%; off-tumor toxicity:0 |
| GBM | EGFRvIII | NCT01454596 | phase 1 | 18 | 2019 | National Cancer Institute, National Institutes of Health | Goff SL, et al [90] |
Median PFS: 1.3 months; Median OS: 6.9 months |
severe hypoxia:2 patients; transient hematologic toxicities: 100% |
| GBM | IL13Rα2 | NCT00730613 | phase 1 | 3 | 2015 | City of Hope Beckman Research Institute and Medical Center, USA | Brown CE, et al [101] | Evidence of a transient antitumor response was observed in two patients. |
107 or 5×107 T cell dose: Grade 3 or higher adverse events:0; 108 T cell dose: one Grade 3 headache, one Grade 3 neurologic- event |
| GBM | IL13Rα2 | NCT02208362 | phase 1 | 1 | 2016 | City of Hope Beckman Research Institute and Medical Center, USA | Brown CE, et al [13] | PFS:7.5 months | toxic effects of grade 3 or higher: none |
| high-grade glioma | IL13Rα2 | NCT02208362 | phase 1 | 58 | 2024 | City of Hope Beckman Research Institute and Medical Center, USA | Brown CE, et al [102] |
Median OS: 8 months; the subset with rGBM:7.7 months; SD or better:50%; PR:2 patients; CR: 1 patient |
Grade 3 and above toxicities:35% |
| GBM | IL13Rα2 | NCT01082926 | phase 1 | 6 | 2022 | City of Hope Beckman Research Institute and Medical Center, USA | Brown CE, et al [103] | four showed signs of transient tumor reduction and/or necrosis | All ≤ grade 3 |
| GBM | HER2 | NCT01109095 | phase 1 | 17 | 2017 | Baylor College of Medicine, Houston Methodist Hospital, and Texas Children’s Hospital, USA | Ahmed N, et al [66] |
Median OS: 11.1 months; PR and SD:8 patients |
NA |
| CNS tumors | HER2 | NCT03500991 | phase 1 | 3 | 2021 | Seattle Children’s Research Institute, USA | Vitanza NA, et al [110] | well tolerated | headache, pain or transient worsening of a baseline neurologic deficit |
| GBM | GD2 | NCT03170141 | phase 1 | 8 | 2023 | Shenzhen Hospital, Southern Medical University, China | Liu Z, et al [118] |
Median OS: 10 months; 3–24 months:50%PR; 6–23 months:37.5% PD; 4 months:12.5% SD |
No severe adverse effects were observed |
| DIPG or spinal cord diff-use DMG | GD2 | NCT04196413 | phase 1 | 4 | 2022 | Stanford Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, USA | Majzner RG, et al [119] | Clinical and radiographic improvement:75% | TIAN |
| H3K27M-mutated DMG; MD; AT/RT | GD2 | NCT04099797 | phase 1 | 11 | 2024 | Baylor College of Medicine, USA | Lin FY, et al [121] |
C7R-GD2 CAR-T: a median duration of neurofunctional improvement:5 months, PR and SD:88%; GD2 CAR-T: duration of neurofunctional improvement for less than 3 weeks |
C7R-GD2 CAR-T: 1 TIAN:88%; CRS:75%; GD2 CAR-T: no CRS and TIAN |
| DIPG | B7H3 | NCT04185038 | phase 1 | 5 | 2023 | Seattle Children’s Research Institute, USA | Vitanza NA, et al [131] | one patient exhibited continuous clinical and radiological improvement over a 12-month follow-up period | headache (3/3), nausea/vomiting (3/3), and fever (3/3),gait disturbance, dysphagia |
| GBM | EphA2 | NCT03423992 | phase 1 | 3 | 2021 | Xuanwu Hospital, Capital Medical University, China | Lin Q, et al [137] |
SD:1 patient; PD:2 patients; OS:86-181d |
2 CRS accompanied by pulmonary edema: 2 patients |
| GBM | EGFRvIII and IL13Rα2 | NCT05168423 | phase 1 | 6 | 2024 | University of Pennsylvania Perelman School of Medicine, USA. | Bagley SJ, et al [150] |
reductions in tumor size:100%; none met criteria for ORR |
Dose-limiting toxicity: 1 patient |
GBM Glioblastoma, OS Overall survival, CRS Cytokine release syndrome, ICANS Immune effector cell-associated neurotoxicity syndrome, PFS Progression-free survival, rGBM Recurrent glioblastoma, SD Stable disease, PR Partial response, CR Complete response, PD Progressive disease, TIAN Tumor-associated inflammatory adverse events, ORR Overall response rate