Table 2. Clinical outcome information for key CAR-T trials in gliomas over the past 5 years.
| Trial and Target | Procedure of CAR-T | Efficacy | IDH status | Other mutations | Lifespan, amplification | Grade 3 or worse adverse events | CRS/ICANS |
|---|---|---|---|---|---|---|---|
| B7-H3 [9] | ICV | PR = 1/18 (6%); SD = 15/18 (83%); PD = 2/18 (11%), Median OS 10.7 months (0.6–45.8) |
1 IDH1 | 1 H3F3A K27M 1 BRAF |
Peak detection at week 3 | 11 | CRS, ICANS not reported |
| GD2 [30] | 1st dose IV; Subsequent doses ICV via Ommaya | Best response PR = 3 (100%) |
0 | 3/3 H3K27M | 2/3 | CRS 3/3, ICANS 1/3, TIAN 3/3 |
|
| GD2 [16] | IV, IV+ICV | PR = 4/8 (50%); SD = 1/8 (13%); PD 3/8 (38%) |
8/8 IDH1/2 wildtype | 7/8 UM MGMT | Expand 1–3 weeks, persisted in peripheral blood at low levels after | 4/8 | CRS, ICANS not reported |
| EphA2 [18] | IV | SD = 1/3 (33%); PD = 2/3 (67%); OS 86–181 days |
- | 3/3 EphA2 | Peaked days 7–13, detectable beyond 28 days | 0/3 | CRS 2/3; ICANS not reported |
| IL-13Ra2 [21] | ICV via Rickham catheter | Median OS 2.9 months | - | 6/6 expressed IL-13Ra2 | - | 0/6 | No CRS, ICANS |
| IL-13Ra2 and EGFR [23] | ICV via Ommaya | 3/6 (50%) SD | 6/6 IDH-wild type | 6/6 EGFR amplification; 1/6 EGFR R108K; 2/6 EGFRvIII; 4/6 UM MGMT, 2/6 Methylated MGMT |
Amplification days 1–7 | 11 | CRS 6/6; ICANS 6/6 |
| IL-13Ra2 [22] | ICV, ICT, ICV+ICT | SD = 29/58 (50%); PR = 2/58 (3%); CR = 1/58 (2%) |
41/58 IDH-wild type | 58/58 IL-13Ra2 | Detected in CSF >7 days post infusion in a subset of patients | 23 | Not reported |
| HER2 [24] | ICV | SD = 1/3 (33%); PD = 2/3 (67%) |
- | 3/3 HER2 | - | 0 | Not reported |
| HER2 [31] | ICV via local injection | SD = 5/9 (56%); PD = 4/9 (44%) |
9/9 IDH wild-type | 5/9 MGMT+, 9/9 HER2 |
- | 7 | 0 CRS, ICANS |
| EGFRvIII [26] | IV | PFS 1.3 months (1.1–1.9); OS 6.9 (1.8–10.0) |
- | 18/18 EGFRvIII | 1 month in 14 patients, 3 months in 5 patients |
18/18 | CRS 1/18, ICANS 0 |
| EGFRvIII and PD-1 [27] | IV | Median OS 11.8 months (9.2–14.2); median PFS 5.2 months (2.9–6.0) |
- | 18/18 EGFRvIII | CAR copies detectable in all at 2 months, longest 7 months | 5 | 0 CRS, ICANS |
| EGFRvIII and EGFR wt [28] | ICV with Ommaya reservoir | SD = 1/3 (33%) | 3/3 IDH wild-type | 3/3 EGFRvIII | - | 2/3 | CRS 3/3, ICANS 3/3; none were Grade 3 or worse |
IV- Intravenous, ICV- Intracerebroventricular, ICT- intratumoural, CRS- cytokine release syndrome, ICANS- immune-effector cell mediated neurotoxicity syndrome. TIAN- tumour inflammation-associated neurotoxicity