Tris-CAR-T Cell Therapy for Recurrent Glioblastoma

Prior treatment

• Receive other drug trials within 60 days before enrollment, or receive other routine treatment in non-experimental designs for glioblastoma, such as stereotactic radiation therapy or placement of carmustine wafers.
• Patients who have received any gene therapy before.

Other illness

• Highly allergic constitution or severe allergies history.
• Those who have psychiatric or psychological diseases and cannot cooperate with treatment and efficacy assessment.
• Combined with infection, active infection, fever of unknown cause.
• Combined with serious or unstable heart, lung, liver, kidney and hematopoietic system diseases, including active hepatitis.
• Combined with inflammation and immune system diseases (such as rheumatoid arthritis), or known immunosuppressive diseases.
• Combined with neurological diseases, such as diffuse leptomeningeal disease, or neurodegenerative diseases.
• Known allergies to immunotherapy and related cellular products.
• Patients with a history of organ transplantation or who are waiting for organ transplantation.

Other

• Kanovsky Performance Status (KPS) ≤ 70.
• Long-term use of immunosuppressants is required for any reason.
• Special cases: pregnancy or lactation.
• Other circumstances in which the investigators believe the patient is unsuitable for this trial.

• Age: 18 years to 70 years (including cut-off values).
• Patients with history of glioblastoma are diagnosed with recurrent glioblastoma and residual tumor after intracranial tumor resection/biopsy performed in Beijing Tiantan Hospital.
• Patients who finished radiotherapy or temozolomide/bevacizumab or other drugs for at least 4 weeks. All toxicities of prior treatment should be defined as less than or equal to grade 1 (except for toxicities such as hair loss or leukoplakia) according to the Common Terminology Standard for Adverse Events (CTCAE 5.0).
• Patients who is suitable for craniotocerebrospinal fluid shunt and attachment (Ommaya device) implantation confirmed by a competent physician.
• Patients and/or legal representative is able to sign written informed consent.
• Kanovsky Performance Status (KPS) ≥ 70.
• According to the researchers' judgment, the life expectancy ≥ 8 weeks.
• White blood cells (WBC) \> 3.50×10\^9/L (performed within 14 days prior to PBMC collection unless otherwise noted).
• Platelet ≥ 200×10\^9/L (performed within 14 days prior to PBMC collection unless otherwise noted).
• Hemoglobin ≥ 120 g/L (performed within 14 days prior to PBMC collection unless otherwise noted).
• Total bilirubin ≤ 20 μmol/L (performed within 14 days prior to PBMC collection unless otherwise noted).
• Aspartic acid aminotransferase (AST) ≤ 2.5×42 U/L (performed within 14 days prior to PBMC collection unless otherwise noted).
• Alanine aminotransferase (ALT) ≤ 2.5×41 U/L (performed within 14 days prior to PBMC collection unless otherwise noted).
• Serum creatinine ≤ 90 μmol/L (performed within 14 days prior to PBMC collection unless otherwise noted).
• Blood oxygen saturation ≥ 95% (performed within 14 days prior to PBMC collection unless otherwise noted).
• Seronegative of the combination of human immunodeficiency virus (HIV) antibody (Ab) (performed within 14 days prior to PBMC collection unless otherwise noted).
• Fertile women: a negative serum pregnancy test (performed within 14 days prior to PBMC collection unless otherwise noted).
• The patient agrees that contraception should be used in patients of childbearing age for at least 3 months from screening to the last infusion of Tris-CAR-T cells. The period of childbearing age is defined as unsurgically neutered (men and women) or without menopause for more than 1 year (women only).