IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Adult Glioblastoma

Inclusion criteria

• (Adult GBM):
• Age ≥ 18 years
• Newly-diagnosed de novo GBM based on the absence of previous history of brain tumor (WHO Grade IV glioma) by histopathology or molecular studies. (secondary GBM not eligible)
• The tumor must have a supratentorial component
• CD70 positive (≥5%, 1+) Tumor expression will be scored on a scale of 0 to 3 staining intensity: 0 = Negative
• = Low level
• = Moderate level
• = High level
• The criteria for inclusion will be at least 5% of the cells scoring 1+ staining intensity (\> 5%, 1+).
• Surgical resection of tumors with less than 3cm x 3cm (9 cm2) residual enhancing tumor as a product of longest perpendicular planes by MRI or biopsy only for tumor measuring less than 3cm x 3cm
• Karnofsky Performance Status (KPS) of \> 70%
• CBC with differential with adequate bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
• Platelet count ≥ 100,000 cells/mm3.
• Hemoglobin ≥ 10 g/dl. (The use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.) • Adequate renal function as defined below:
• BUN ≤ 25 mg/dl
• Creatinine ≤ 1.7 mg/dl • Adequate hepatic function as defined below:
• Bilirubin ≤ 2.0 mg/dl
• ALT ≤ 5 times institutional upper limits of normal for age
• AST ≤ 5 times institutional upper limits of normal for age
• Signed informed consent. If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the legally authorized representative.
• For females of childbearing potential, a negative serum pregnancy test at enrollment.
• Women of childbearing potential (WOCBP) must be willing to use an acceptable contraceptive method to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
• Males with female partners of childbearing potential must agree to practice adequate contraceptive methods throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.

Exclusion criteria

• (Adult GBM):
• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3years. (In situ cancer are permissible)
• Metastases detected below the tentorium or beyond the cranial vault
• Leptomeningeal disease beyond the cranial vault. (Focal, adjacent and leptomeningeal involvement is allowable at the discretion of the PI).
• Recurrent or multifocal malignant gliomas.
• The patient is not a candidate for cellular therapy as assessed by the study bone marrow transplant physician.
• Known immunosuppressive disease or human immunodeficiency virus (HIV) infection. Rationale: The need to exclude patients with the immunosuppressive disease or human
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization.
• Transmural myocardial infarction within the last 6 months.
• Acute bacterial or fungal infection requiring intravenous antibiotics at the initiation of XRT/TMZ.
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the initiation of XRT/TMZ.
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
• Patients with an autoimmune disease requiring medical management with immunosuppressants.
• Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.
• Active connective tissue disorders such as lupus or scleroderma that, in the investigator's opinion, place the patient at high risk for radiation toxicity.
• Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant.
• Patients treated on any other therapeutic clinical protocols within 30 days prior to enrollment.