TIL Therapy Combined With Pembrolizumab for Advanced Brain Cancer Including Gliomas and Meningiomas

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 standardtreatment regimens available.

• Test subjects must have tumor regions eligible for biopsy or resection, or malignantbody 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 anticoagulanttherapy within the previous 3 days)

• International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapywithin 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 approvedhighly effective methods of contraception at the time of informed consent andcontinue within 1 year after the completion of lymphodepletion

• Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy, andbiologics 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 (orequivalent doses of hormones) or outoimmune diseases requiring immunomodulatorytreatment

• Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity ofthe 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 ejectionfraction less than 35%; Severe cardiac rhythm and conduction anomaly, such asventricular arrhythmia requiring clinical intervention, second-third degreeatrioventricular conductive block, etc.

• Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, activeHBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infectionor Treponema pallidum antibody positive.

• Severe physical or mental diseases;

• Have a systemic active infection requiring treatment, or have positive bloodcultures(or imaging evidence of infection).

• Having been treated within a month or being treated now with other medicines, orother biologic therapy, chemo-or radiotherapy.

• History of allergy to chemical compounds consisting of chemical and biologicalsubstances 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 alopeciaexcluded).

• Females in pregnancy or lactation. History of organ transplantation, allogeneic stemcell transplantation, and renal replacement therapy.

• Researchers consider the test subject as having a history of other severe systemicdiseases, or other reasons inappropriate for the clinical study.