Intracranial Genetically Modified Immune Cells (TGFβR2KO/IL13Rα2 CAR T-Cells) for the Treatment of Recurrent or Progressive Glioblastoma or Grade 3 or 4 IDH-Mutant Astrocytoma

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorizedrepresentative

• Note: For research participants who do not speak English, a short form consentmay be used with a City of Hope (COH) certified interpreter/translator toproceed with screening and leukapheresis, while the request for a translatedmain consent is processed. However, the research participant is allowed toproceed with surgery/Rickham placement and CAR T cell infusion only after thetranslated main consent form is signed

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies. Ifunavailable, exceptions may be granted with study principal investigator (PI)approval

• Age: ≥ 18 years

• Karnofsky performance status (KPS) ≥ 70%, Eastern Cooperative Oncology Group (ECOG) ≤ 2

• Life expectancy ≥ 4 weeks

• If the participant has a shunt, they must be informed of the following:

• If the shunt is not programmable, the participant must be willing to have aprogrammable shunt placed prior to CAR T cell infusion, and

• If the shunt is programmable, in order to proceed to the treatment portion ofthe study, the participant must be able to tolerate their shunt beingfunctionally closed for at least 2 hours

• Participant has a prior histologically-confirmed diagnosis of a grade 3 or 4IDH-mutant astrocytoma or glioblastoma, or has a prior histologically-confirmeddiagnosis of a grade 2 or 3 astrocytoma and now has radiographic progressionconsistent with grade 3 or 4 IDH-mutant astrocytoma

• Relapsed disease: radiographic evidence of recurrence/progression of measurabledisease after standard therapy, and ≥ 12 weeks after completion of front-lineradiation therapy

• COH clinical pathology confirms IL13Rα2+ tumor expression by immunohistochemistry (H-score ≥ 80)

• No known contraindications to leukapheresis, steroids, or tocilizumab

• White blood cell (WBC) > 2000 /dl (or absolute neutrophil count [ANC] ≥ 1,000/mm^3) (to be performed within 14 days prior to leukapheresis unless otherwise stated)

• Platelets ≥ 75,000/mm^3 (to be performed within 14 days prior to leukapheresisunless otherwise stated)

• Hemoglobin ≥ 8g/dl (to be performed within 14 days prior to leukapheresis unlessotherwise stated)

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (to be performed within 14 daysprior to leukapheresis unless otherwise stated)

• Aspartate aminotransferase (AST) ≤ 2.5 x ULN (to be performed within 14 days priorto leukapheresis unless otherwise stated)

• Alanine aminotransferase (ALT) ≤ 2.5 x ULN (to be performed within 14 days prior toleukapheresis unless otherwise stated)

• Serum creatinine ≤ 1.6 mg/dL (to be performed within 14 days prior to leukapheresisunless otherwise stated)

• Oxygen (O2) saturation ≥ 95% on room air (to be performed within 14 days prior toleukapheresis unless otherwise stated)

• Seronegative for HIV antigen/antibody (Ag/Ab) combo, hepatitis C virus (HCV), activehepatitis B virus (HBV) (surface antigen negative) (to be performed within 14 daysprior to leukapheresis unless otherwise stated)

• Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test (tobe performed within 14 days prior to leukapheresis unless otherwise stated)

• If the urine test is positive or cannot be confirmed as negative, a serumpregnancy test will be required

• Agreement by females and males of childbearing potential to use an effective methodof birth control or abstain from heterosexual activity for the course of the studythrough at least 3 months after the last dose of protocol therapy

• Childbearing potential defined as not being surgically sterilized (men andwomen) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

• Owing to higher frequency of wound-related complications, participants who requireactive bevacizumab therapy at the time of enrollment are excluded

• Participant has not yet recovered from toxicities of prior therapy

• Uncontrolled seizure activity and/or clinically evident progressive encephalopathy

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to study agent

• Clinically significant uncontrolled illness

• Active autoimmune disease requiring systemic immunosuppressive therapy

• Active infection requiring intravenous (IV) antibiotics (e.g., minor scalp infectionis not an exclusion)

• Known history of human immunodeficiency virus (HIV) or hepatitis B or hepatitis Cinfection

• Other active malignancy. Note: Patients with a prior or concurrent malignancy whosenatural history or treatment does not have the potential to interfere with thesafety or efficacy assessment of the investigational regimen are eligible for thistrial

• Females only: Pregnant or breastfeeding

• Any other condition that would, in the investigator's judgment, contraindicate thepatient's participation in the clinical study due to safety concerns with clinicalstudy procedures

• Prospective participants who, in the opinion of the investigator, may not be able tocomply with all study procedures (including compliance issues related tofeasibility/logistics)