Clinical Trial Finder

Inclusion Criteria:

1. abilities to understand and the willingness to provide written informed consent; 2. patients are ≥ 1 and ≤ 80 years old; 3. recurrent glioblastoma or brain tumor patients with measurable tumors. Patients have received standard care of medication, such as gross total resection with concurrent radio-chemotherapy (~54

• - 60 Gy, TMZ).

Patients must either not be receiving dexamethasone or receiving ≤ 4 mg/day at the time of leukopheresis; 4. Malignant cells are target antigen positive confirmed by immunostaining, quantitative PCR or sequencing; 5. karnofsky performance score (KPS) ≥ 60; 6. life expectancy >3 months; 7. satisfactory bone marrow, liver and kidney functions as defined by the following: absolute neutrophile count ≥ 1500/mm^3; hemoglobin > 10 g/dL; platelets > 100000 /mm^3; Bilirubin < 1.5×ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5×ULN; creatinine < 1.5×ULN; 8. peripheral blood absolute lymphocyte count must be above 0.8×10^9/L; 9. satisfactory heart functions; 10. patients must be willing to follow the orders of doctors; 11. women of reproductive potential (between 15 and 49 years old) must have a negative pregnancy test within 7 days of study start. Male and female patients of reproductive potential must agree to use birth control during the study and 3 months post study.

Exclusion Criteria:

1. a prior history of gliadel implantation 4 weeks before this study start or antibody based therapies; 2. HIV positive; 3. tuberculosis infection not under control; 4. history of autoimmune disease, or other diseases require long-term administration of steroids or immunosuppressive therapies; 5. history of allergic disease, or allergy to immune cells or study product excipients; 6. patients already enrolled in other immune cell clinical study; 7. patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Background: Glioblastoma multiforme (GBM) is the most dangerous and aggressive form of brain cancer. Chimeric antigen receptor (CAR)-modified T cells have been shown to mediate long-term durable remissions in recurrent or refractory CD19+ B cell malignancies, and thus the CAR-T therapy approach is considered a promising treatment against GBM. Certain antigens are highly specific in GBM, such as epidermal growth factor receptor variant iii, EGFRviii. EGFRviii is a variant form of EGFR protein, and one of the potential target antigens in GBM. Alternative antigens such as GD2 and MucI have also been targeted as potential GBM antigens. Tumor microenvironment is known to suppressive anti-cancer immune responses. Many immune checkpoint inhibitors have demonstrated marked anti-tumor activities. Instead of infusing antibodies, this study aims to infuse antigen-specific T cells modified with immune modulatory genes (IgT) such as genes encoding immune checkpoint inhibitors. Combination of tumor targeting and immune modulatory activities, the IgT cells could target both the tumor cells and the tumor microenvironment.

Arms

Experimental: Antigen-specific IgT cells

Patients will receive non-myeloablative chemotherapy consisting of fludarabine and/or cyclophosphamide, followed by intravenous infusion of autologous IgT cells. A standard 3+3 escalation approach will be used to obtain the safe dosage of IgT cells. The tested IgT cell dosage ranges from 0.5×10^5 /kg to 2.5×10^7 /kg

Interventions

Biological: - Antigen-specific IgT cells

Tumor antigen-specific IgT cells are infused intravenously or directly to the tumor location of the patients in a three-day split-dose regimen（day 0,10%; day1, 30%; day2, 60%）to complete a total targeted dose. Drug: cyclophosphamide 250 mg/m^2 d1-3; Drug: Fludarabine 25mg/m^2 d1-3