B7-H3 is expressed at low levels in normal tissues but overexpressed in various tumor tissues. The ubiquitous expression of B7-H3 in tumors of different grades is a key feature for brain gliomas. The immunohistochemistry study showed that B7-H3 is abundantly expressed on both glioma (especially high-grade glioma) cells and tumor-associated endothelial cells. For GBM, the expression of B7-H3 is intensely positive, especially on tumor cells and vascular endothelial cells, which makes B7-H3 a potential immunotherapeutic target. γδ T cells recognize tumor cells without being restricted by MHC molecules, and thus can be used in allogeneic therapy without the risk of causing graft-versus-host disease. This study is an open-label, single-arm, dose-escalation and dose-expansion clinical study aimed at evaluating the safety and efficacy of allogeneic B7-H3 CAR γδT in patients with malignant glioma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Dose escalation (3+3) : dose 1 (1 × 10\^7 CAR+cells) , dose 2 (3 × 10\^7 CAR+cells), dose 3 (6× 10\^7 CAR+cells), once every 4 weeks via an Ommaya reservoir or intrathecal administration. Dose expansion 1: dose of RP2D, once every 4 weeks via an Ommaya reservoir or intrathecal administration. Dose expansion 2: 3 × 10\^7 CAR+cells, every two weeks for three consecutive months, then changed to once every 4 weeks via an Ommaya reservoir or intrathecal administration.
Dushu Lake Hospital Affiliated to Soochow University
Suzhou, Jiangsu, China
RECRUITINGPhase 1: Incidence of Adverse Events (AEs)
AE is defined as any adverse medical event from the date of the cell infusion to 12 months after B7-H3 CAR-γδT cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versus-host disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.
Time frame: 12 months
Phase 1:Incidence of Dose-Limiting Toxicities (DLTs)
DLT was defined as B7-H3 CAR-γδT cells-related events with onset within first 28 days following infusion
Time frame: 28 days after the first dose of B7-H3 CAR-γδT cells
Phase 1:Maximum tolerated dose (MTD)
Time frame: 28 days after the first dose of B7-H3 CAR-γδT cells
Phase 1: Recommended phase 2 dose (RP2D)
Time frame: 28 days after the first dose of B7-H3 CAR-γδT cells
Pharmacokinetics: copy number of B7-H3 CAR-γδT cells in cerebrospinal fluid(CSF)
Time frame: 28 days after the first dose of B7-H3 CAR-γδT cells
Pharmacodynamics: Peak level of cytokines in CSF
Time frame: 28 days after the first dose of B7-H3 CAR-γδT cells
Phase 2: Overall survival (OS)
Time frame: 6 months, 9 months and 12 months
Phase 2: Progression Free Survival (PFS)
Time frame: 6 months
Disease Control Rate (DCR)
Time frame: 6 months
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