Combining TIL Therapy and Pembrolizumab for Advanced Brain Cancer

Inclusion Criteria:

* Age: 16 years to 90 years
* Histologically diagnosed as primary/relapsed/metastasized brain glioma
* Expected life span more than 3 months
* Karnofsky≥60% or ECOG score 0-2
* Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
* Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated
* At least 1 evaluable tumor lesion
* Hematology and Chemistry（within 7 days prior to enrollment）:
* Absolute count of white blood cells≥2.5×10\^9/L
* Absolute count of neutropils≥1.5×10\^9/L
* Absolute count of lymphocytes ≥0.7×109/L
* Platelet count≥100×10\^9
* hemoglobin≥90 g/L
* Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days)
* International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days)
* Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min
* Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN)
* Totol bilirubin≤1.5×ULN
* No absolute or relative contraindications to operation or biopsy
* Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent and continue within 1 year after the completion of lymphodepletion
* Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy, and biologics must cease 28 days before obtaining TILs
* Be able to understand and sign the informed consent document;
* Be able to stick to follow-up visit plan and other requirements in the agreement.

Exclusion Criteria:

* Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment
* Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%
* Significant cardiovascular anomalies according to any of the following definitions:
* New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant
* Low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrioventricular conductive block, etc.
* Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive.
* Severe physical or mental diseases;
* Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection).
* Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy.
* History of allergy to chemical compounds consisting of chemical and biological substances resembling cell therapy.
* Having received immunotherapy and developed an irAE level greater than Level 3.
* Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded).
* Females in pregnancy or lactation. History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy.
* Researchers consider the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.