Personalized Chimeric Antigen Receptor T Cell Immunotherapy for Patients With Recurrent Malignant Gliomas

A Pilot Study to Evaluate the Safety and Efficacy of Personalized Chimeric Antigen Receptor T Cell Immunotherapy for Patients With Recurrent Malignant Gliomas Based on the Expression of Tumor Specific/Associated Antigens

A pilot study to determine the safety and efficacy of chimeric antigen receptor T cell (autologous T cells transduced with a lentiviral vector expressing chimeric antigen receptor with or without anti-PDL1 antibody) personalized immunotherapy for patients with recurrent malignant gliomas based on the expression of tumor specific/associated antigens (EGFRVIII, IL13Rα2, Her-2, EphA2, CD133, GD2).

Inclusion Criteria:

• Voluntary informed consent for entry of trial;

• Age greater than 18 years, and less than 70 years;

• Pathologically confirmed recurrent malignant gliomas;

• Tumor cells from resected tissue must be available for antigen testing (EGFRvIII, IL13Rα2, Her-2, CD133, EphA2, GD2) and at least one of the targets should be tested positively by immunohistochemistry study;

• If the patient is on dexamethasone, the anticipated dose must be 4 mg/day or less for at least 5 days prior to apheresis.

• Patients must have a Karnofsky performance status of greater than or equal to 70.

• Life expectancy greater than 3 months;

• Participants with adequate organ function as measured by:

  1. White blood count greater than or equal to 2500/mm^3; platelets greater than or equal to 100,000/mm^3, hemoglobin greater than or equal to 10.0 g/dL; without transfusion or growth factor support
  2. Aspartate transaminase (AST), Alanine transaminase (ALT), gamma glutamyl transpeptidase (GGT), lactic acid dehydrogenase (LDH), alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin less than or equal to 2.0 mg/dL
  3. Serum creatinine less than or equal to 1.5 x upper limit of normal
  4. Coagulation tests prothrombin time (PT) and partial thromboplastin time (PTT) have to be within normal limits, unless the patient has been therapeutically anti-coagulated for previous venous thrombosis.

Exclusion Criteria:

• Female subjects of reproductive potential who are pregnant or lactating;
• Previous treatment with any gene therapy products or other form immunotherapy;
• Uncontrolled active infection.
• Active or latent chronic hepatitis B [detectable hepatitis B surface antigen (HBsAg)] or active hepatitis C (positive serology [hepatitis C virus Ab]) infection.
• HIV infection;
• History of allergy or hypersensitivity to study product excipients (human serum albumin, Dimethyl sulfoxide, and Dextran 40);
• Currently enrolled in other clinical trials;