Table 1.
First‐in‐human clinical experience with CAR‐T therapy for glioblastoma
| Target antigen | Trial | Aim | CAR T product | Route of delivery | Antigen loss | TME | Toxicity | Patient outcome |
|---|---|---|---|---|---|---|---|---|
| IL13Rα2 |
NCT00730613 City of Hope66, 68 |
First to evaluate intracranial delivery of IL13Rα2 CAR in rGBM |
IL13(E13Y)‐CD3ζ CD8+ CTL clones |
ICT | YES: IL13Rα2 negative/low (1 patient tested) | Transient inflammatory response/necrosis at tumor site by MRI | No DLTs |
3 pts evaluated Median OS 10.9 mo Increased necrotic volume at treatment site (1 pt) Decreased IL13Rα2 expression (1 pt) |
| IL13Rα2 |
NCT01082926 City of Hope67 |
First off‐the‐shelf allogeneic CAR T cells for rGBM. Evaluated feasibility of [18F]FHBG gene reporter imaging to monitor T‐cell distribution in rGBM |
IL13(E13Y)‐CD3ζ [18F]FHBG HSV1‐tk Glucocorticoid‐receptor‐depleted allogeneic CD8+ CTL clone |
ICT | Not reported | Not reported | No DLTs |
6 pts evaluated [18F]FHBG gene reporter allowed longitudinal imaging of ICT CAR‐T Clinical outcomes not reported |
| IL13Rα2 |
NCT02208362 City of Hope69 |
Evaluate safety of ICV and dual ICT‐ICV CAR delivery in rGBM |
IL13(E13Y)‐41BBζ Memory‐derived T cells |
ICT, ICV and dual ICT‐ICV | YES: IL13Rα2 negative/low tumors (1 patient reported) | Increased CD3+ CD14+ and CD15+ immune cells and inflammatory cytokines | No DLTs | Case study demonstrated CAR‐Ts mediate complete response that was durable for 7.5 mo |
| EGFRvIII |
NCT02209376 UPenn80 |
To determine safety and efficacy of single‐dose IV EGFRvIII CAR‐T in rGBM |
EGFRVIII‐41BBζ Bulk T cells |
IV | YES: EGFRvIII decreased in 5/7 patients | Increased IDO, FOXP3, IL‐10, PD‐L1 and TGFβ | No DLTs |
10 pts evaluated Median OS 8.3 mo 1/10 extended SD, alive @ 18 mo Decreased EGFRvIII expression (5 of 7 pts) |
| EGFRvIII |
NCT01454596 NCI81 |
To determine MTD and DLT of IV EGFRvIII CAR‐T and IL‐2 following lymphodepletion in rGBM |
EGFRvIII‐CD28‐41BBζ Bulk T cells |
IV | Not evaluated | Not evaluated |
2 DLTs 1 grade 5 at highest dose |
18 pts evaluated Median PFS 1.3 mo Median OS 6.9 mo 1/18 pts median PFS of 12.5 mo and alive at 59 mo |
| HER2 |
NCT01109095 Baylor, TX260 |
To determine safety and activity of HER2 CAR‐Tin adult and pediatric rGBM |
HER2‐CD28ζ VST: (EBV‐CMV‐AD) |
IV | Not evaluated | Not evaluated | No DLTs |
16 pts evaluated Median OS 11.1 mo 1/16 PR 7/16 SD (3 extended SD) |
Abbreviations: CAR, chimeric antigen receptors; DLT, dose limiting toxicity; ICT, intra‐cranial tumoral; ICV, intra‐cranial ventricular; IV, intravenous; rGBM, recurrent glioblastoma; VST, virus specific T cells.