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INCLUSION CRITERIA. 1. Karnofsky score of > 60% 2. Diagnosis of recurrent supratentorial- or infra-tentorial glioblastoma multiforme (GBM) (World Health Organization 2016 or 2021), based on Response assessment in neuro-oncology criteria (RANO) magnetic resonance imaging (MRI) criteria. Disseminated GBM down the spinal cord is not allowed. Must have previously undergone resection or biopsy at initial diagnosis. 3. Must have undergone at least 4005 cGy of radiation with concurrent temozolomide. 4. No current or previous exposure to antiangiogenic agents, such as bevacizumab. 5. Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study treatment discontinuation. 6. Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the cell infusion therapy. If a male subject receives multiple infusions, they must remain on contraception throughout the duration and 3 months after the last cell infusion therapy. 7. The subject is willing and able to comply with study procedures based on the judgment of the investigator. EXCLUSION CRITERIA. 1. Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study). 2. Subjects with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen. 3. Active infection with HIV, hepatitis B virus, hepatitis C virus (HCV). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibodies, negative for Hepatitis B surface antigen, and negative for HCV antibody and viral load. 4. Contraindication to MRI contrast agents or an inability to undergo MRI scans due to MRI non-compatible implanted materials. 5. Prior exposure to chimeric antigen receptor T cell therapy for treatment of glioblastoma. 6. Evidence of disseminated disease involving the brainstem, cerebellum or spinal cord. 7. Previously implanted carmustine wafers or brachytherapy for the treatment of glioma.

This is a phase 1, single center, open-label study aims to determine the safety of escalating doses of chimeric antigen receptor T cells (CAR-T) cells targeting the B7-H3 antigen administered via intraventricular infusion to adult subjects with relapsed or refractory glioblastoma (GBM). Subjects with GBM who meet procurement eligibility criteria will have cells collected following their initial surgical resection to manufacture CAR.B7-H3T cells, preferably prior to initiation of adjuvant chemoradiation. At the time that the subjects have confirmed refractory or recurrent GBM, CAR.B7-H3T cells will be manufactured for subjects who likely to be eligible for cell infusion. Eligible subjects will receive up to 3 weekly infusions of CAR.B7-H3 cells. To receive the additional cycles of CAR.B7-H3 cells, all treatment-related toxicities must have resolved to grade < 3, the subject must not have experienced a dose limiting toxicity (DLT) and the subject must not have progressive disease that has been confirmed by magnetic resonance imaging per Immunotherapy response assessment in neuro-oncology criteria. The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided on based on the maximum tolerated dose (MTD) and additional factors such as the feasibility of administering infusions.

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