CAR T cells: engineered immune cells to treat brain cancers and beyond

Huang, Zoufang; Dewanjee, Saikat; Chakraborty, Pratik; Jha, Niraj Kumar; Dey, Abhijit; Gangopadhyay, Moumita; Chen, Xuan-Yu; Wang, Jian; Jha, Saurabh Kumar

doi:10.1186/s12943-022-01712-8

Molecular Cancer

Table 2 Clinical trials on CAR T-based management of brain cancer

From: CAR T cells: engineered immune cells to treat brain cancers and beyond

S no.	Targets	Phases	Status	Indications	CAR designs	Administration routes	Comments	Identifiers
1	IL3Rα2	I	Completed	Recurrent/refractory malignant glioma	IL13-CD3ζ CD8+ cytotoxic T-lymphocyte clones	Intracranial	Transient inflammatory response, necrosis at tumor site, antigen loss	NCT00730613 [79]
2	IL3Rα2	I	Completed	Recurrent/refractory malignant glioma	IL-13 zetakine	Intratumoral infusion	No dose-limiting toxicity	NCT01082926 [80]
3	IL3Rα2	I	Ongoing	Recurrent/refractory malignant glioma	IL-13–4-1BBζ memory-derived T cells	Intracranial, intraventricular	Complete clinical response up to 7.5 months, antigen loss	NCT02208362 [82]
4	IL3Rα2	I	Ongoing	Leptomeningeal glioblastoma, ependymoma, or medulloblastoma	IL3Rα2-specific CAR with 4-1BB co-stimulation	Intraventricular	Evaluation of safety, feasibility, persistence, expansion	NCT04661384 [83]
5	IL3Rα2	I	Ongoing	Recurrent/refractory pediatric brain tumors	IL3Rα2-specific CAR	Intraventricular	Assessment of side effects, after lymphodepletion	NCT04510051 [84]
6	IL3Rα2	I	Ongoing	Glioblastoma	IL3Rα2-targeted CAR	Intraventricular, intratumoral	Trial for combination therapy with checkpoint inhibitor	NCT04003649 [134]
7	EGFRvIII	I, II	Completed	Malignant glioma	EGFRvIII-CD28–4-1BBζ Bulk T cells	Intravenous	Progression-free survival uup to12.5 months, dose-limiting toxicity at higher doses	NCT01454596 [86]
8	EGFRvIII	I	Terminated	Glioblastoma	EGFRVIII-4-1BBζ CAR	Intravenous	Increased IDO, FOXP3, IL-10, PD-L1 and TGFβ, antigen loss	NCT02209376 [90]
9	EGFRvIII	I	Completed	Glioblastoma	EGFrvIII-specific CAR T expressing 4-1BB and TCRζ	Intravenous	Result has not yet been published	NCT03726515 [92]
10	EGFRvIII	I	Terminated	Glioma grade IV	EGFRvIII CAR	Systemic	Radiolabelling of CAR T cells	NCT02664363 [136]
11	EGFRvIII	I	Terminated	Recurrent glioblastoma	EGFRvIII-targeted CAR	Intracerebral	Recruitment halted	NCT03283631 [174]
12	EGFR806	I	Ongoing	Recurrent/refractory EGFR+ pediatric CNS tumors	EGFR806-specific CAR	Delivered into tumor cavity or ventricular system	Evaluation of safety, efficacy, tolerability, distribution, tumor response	NCT03638167 [94]
13	EGFR806	I	Ongoing	Solid tumors including neuroblastoma	EGFR806-specific CAR	Systemic	Assessment of on target off tumor toxicity	NCT03618381 [95]
14	HER2	I	Completed	Glioblastoma	HER2-CD28ζ virus-specific T cells	Intravenous	No dose limiting toxicity	NCT01109095 [100]
15	HER2	I	Ongoing	Recurrent/refractory glioblastoma grade III/IV	HER2-specific, hinge-optimized, 4-1BB-co-stimulatory chimeric receptor	Intracerebral	Investigation on side effects and best suit dose	NCT03389230 [102]
16	HER2	I	Ongoing	Metastatic meningeal neoplasm	HER2-specific CAR	Intraventricular	Evaluation of side effects, best dose	NCT03696030 [103]
17	HER2	I	Ongoing	Recurrent/refractory HER2+ pediatric CNS tumors	HER2-specific CAR	Intracerebral	Evaluation of safety, efficacy, distribution	NCT03500991 [105]
18	HER2	I	Ongoing	HER2+ CNS tumors	HER2-specific CAR	Intracranial	Evaluation of efficacy, side effects, largest safe dose	NCT02442297 [106]
19	HER2	I	Ongoing	Pediatric recurrent/refractory ependymoma	HER2-specific CAR	Intravenous	Evaluation of safety and feasibility	NCT04903080 [107]
20	B7-H3	I, II	Ongoing	Recurrent/refractory glioblastoma	B7-H3-targeted CAR	Intratumoral, intraventricular	Concurrent therapy with temozolomide	NCT04077866 [111]
21	B7-H3	I	Ongoing	Diffuse intrinsic pontine glioma/diffuse midline glioma and recurrent or refractory pediatric central nervous system tumors	B7-H3-specific CAR	Delivered into tumor cavity or ventricular system	Assessment of safety, distribution, peripheral trafficking	NCT04185038 [112]
22	B7-H3	I	Unknown	Recurrent/refractory glioblastoma	B7-H3-targeted CAR	Intratumoral, intraventricular	Unknown status after May 2020	NCT04385173 [175]
23	CD147	I	Unknown	Malignant glioma	CD147 CAR T cells	Intracavity injection	Unknown status after May 2020	NCT04045847 [114]
24	GD2	I	Completed	Recurrent/refractory neuroblastoma	Anti-GD2 CAR	Systemic	No disease progression with detectable CAR levels upto 45 days	NCT02761915 [120]
25	GD2	I	Ongoing	GD2+ brain tumor	C7R-GD2.CAR T Cells	Intravenous	Ongoing safety and efficacy assessment	NCT04099797 [121]
26	GD2	I, II	Ongoing	Recurrent/refractory neuroblastoma	Anti-GD2 CAR T cells	Systemic	Dose escalation and expansion trial	NCT03373097 [122]
27	GD2	I	Ongoing	Intrinsic pontine glioma, spinal diffuse midline glioma	GD2-specific CAR	Intravenous	Assesment of safety, feasibility, recommendation of dose for phase II trial	NCT04196413 [123]
28	GD2	I	Ongoing	Pediatric neuroblastoma	GD2-specific CAR with autologous NKT cells expressing IL-15	Systemic	The first trial on GD2 expressing NKT cells	NCT03294954 [135]
29	EphA2	I, II	Withdrawn	Malignant glioma	EphA2-specific CAR	Systemic	Trial withdrawn	NCT02575261 [131]
30	CLTX	I	Ongoing	MMP2+ recurrent or progressive glioblastoma	CLTX (EQ)-CD28-CD3 zeta-CD19t-expressing CAR T lymphocytes	Intravenous	Tumor binding peptide used as targeting domain	NCT04214392 [127]
31	CD171	I	Ongoing	Neuroblastoma	CD171-specific CAR T cells expressing EGFR1	Systemic	Assessment for maximum tolerable dose	NCT02311621 [129]
32	NKG2D	I	Withdrawn	Solid tumors including glioblastoma	NKG2D-based CAR	Intravenous, intra-arterial	Trial withdrawn	NCT04270461 [142]
33	EGFRvIII, IL13Rα2, HER2, CD133, EphA2 or GD2	I	Ongoing	Recurrent malignant glioma	Biological, antigen-specific CAR T cells	Systemic delivery of lentiviral vector	Personalized CAR design based on tumor antigen expression	NCT03423992 [176]

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