Temporarily suspended for HGRAC filing requirements

This is a dose exploration clinical trial to assess the safety and feasibility of the IL13Ra2-targeted CAR-T in glioma.

Interleukin 13 receptor subunit alpha-2 (IL13Ra2A) is a high-affinity membrane receptor of the anti-inflammatory Th2 cytokine IL13, which is overexpressed in glioma and correlated with poor prognosis.

Chimeric antigen receptor (CAR) T cell therapy is a promising treatment approach for many malignancies. IL13Ra2-targeted CAR-T cells are under investigation in several clinical trials in primary CNS malignancies.

The investigators now designed a new structure CAR targeted IL13Ra2, and initiated a single arm, open, dose exploration clinical trial to evaluate the safety, tolerability, clinical efficacy, and pharmacokinetic characteristics of IL13Rα2 CAR-T for patients with glioma. This clinical trial will enroll 12-30 cases of patients with IL13α2-positive recurrent or refractory WHO grade 4 glioma (r/r WHO4 glioma), aiming to find the maximum tolerable dose (MTD), the recommended phase 2 dose (RP2D) and preliminary efficacy of the new structure IL13Ra2 CAR-T.

Inclusion criteria:

1. Male or female aged 18-75 years (including 18 and 75 years old).
2. Karnofsky scale score (KPS)≥50.
3. Subjects with WHO grade 4 gliomas who have relapsed or progressed during or after standard treatments such as surgery, radiotherapy, and chemotherapy.
4. Tumor with IL13Rα2 positive expression.
5. Availability in collecting peripheral blood mononuclear cells (PBMCs).
6. Adequate laboratory values and adequate organ function.
7. Patients with childbearing/fathering potential must agree to use highly effective contraception.

Exclusion criteria:

1. Pregnant or breastfeeding females.
2. Contraindication to bevacizumab.
3. Within 5 days prior to the infusion of CAR-T cells, subjects receiving systemic administration of steroids with dosage more than 10mg/d prednisone or the equivalent doses of other steroids (not including inhaled corticosteroid).
4. Comorbid with other uncontrolled malignancy.
5. Active immunodeficiency virus (HIV) or hepatitis B virus or hepatitis C virus or tuberculosis infection.
6. Autoimmune diseases.
7. Severe or uncontrolled psychiatric diseases or condition that could increase adverse events or interfere the evaluation of outcomes.
8. Subjects who have previously received cell therapy (such as TCR-T, CAR-T, TIL, etc.).
9. Subjects with other conditions that would interfere trial participation at the investigator's discretion.