Locoregional Administration of Genetically Engineered Cells (EGFR/IL13Rα2 Pool-CAR T Cells) for the Treatment of Recurrent or Progressive High-Grade Gliomas

Main Inclusion Criteria

* Documented informed consent of the participant and/or legally authorized representative.
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with Study PI approval.
* Age 18 years and older.
* KPS ≥ 70%, ECOG ≤ 2 (Appendix A).
* Life expectancy ≥ 4 weeks.
* Participant has a prior histologically confirmed diagnosis of a glioblastoma (IDH-wildtype) or grade 4 IDH-mutant astrocytoma, or has a prior histologically confirmed diagnosis of a grade 2 or 3 astrocytoma and now has radiographic progression consistent with grade 4 IDH-mutant astrocytoma.
* Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy (such as temozolomide with or without Optune device), and ≥ 12 weeks after completion of front-line radiation therapy.
* COH Clinical Pathology assessment at the initial tumor presentation or recurrent disease (reference Appendix B):

  * IL13Rα2+ expression by IHC \> 20, and
  * EGFR gene-altered by NGS or FISH analysis
* No known contraindications to leukapheresis, steroids, imaging studies, or tocilizumab.
* WBC \> 2000 /dl (or ANC ≥ 1,000/mm3)
* Platelets ≥ 75,000/mm3
* Hemoglobin \> 9g/dL
* Total bilirubin ≤ 1.5x ULN
* AST ≤ 2.5x ULN
* ALT ≤ 2.5x ULN
* Serum creatinine ≤1.6 mg/dL
* O2 saturation ≥ 95% on room air.
* Seronegative for HIV Ag/Ab combo, HCV, and active HBV
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test.
* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of CAR T cells.

Main Exclusion Criteria

* Owing to higher frequency of wound-related complications, participants who require active bevacizumab therapy at the time of enrollment are excluded.
* Participant has not yet recovered from toxicities of prior therapy.
* Participant has received any live vaccine within 30 days prior to enrollment.
* Uncontrolled seizure activity and/or clinically evident progressive encephalopathy.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
* Clinically significant uncontrolled illness.
* Active autoimmune disease requiring systemic immunosuppressive therapy
* Active infection requiring IV antibiotics (for example, minor scalp infection is not exclusion).
* Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection.
* Other active malignancy.
* Females only: Pregnant or breastfeeding.
* Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures.
* Prospective participants who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).