• Safety Run In Arm and ARM 1: Recurrent GBM, EGFRvIII mutant

⁃ Participants must have histologically confirmed recurrent GBM or molecular features of GBM with presence of EGFRvIII mutation within 30 days of consent. MGMT methylated, unmethylated, or unknown is allowed.

⁃ Participants must be at first progression or recurrence and have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated.

‣ Participants must be 4 weeks from prior alkylating therapy or immunotherapy and ≥ 5 half-lives from another investigational agent. No washout is required from radiation since participants will need histological confirmation of recurrence to participate.

⁃ ARM 2: Newly Diagnosed GBM, EGFRvIII mutant

∙ Participants must have histologically confirmed newly diagnosed GBM with presence of EGFRvIII mutation and their tumors must be MGMT unmethylated.

‣ Treatment planned with involved field radiation alone without concomitant or sequential temozolomide.

⁃ ARM 3: Recurrent GBM, EGFRvIII negative (will only open once safety is confirmed in Arms 1 and 2)

∙ Participants must have histologically confirmed recurrent GBM with absence of EGFRvIII mutation within 30 days of consent but with EGFR amplification.

‣ Participants must be at first recurrence and have at least received prior radiation. Prior temozolomide is not required if the participant is MGMT unmethylated. Participants must be 4 weeks from prior alkylating therapy or immunotherapy and ≥ 5 half-lives from another investigational agent. No washout is required from radiation since participants will need histological confirmation of recurrence to participate.

⁃ ALL ARMS:

∙ Participants must have measurable disease, defined as at least one lesion ≥10 mm (≥1 cm) with MRI. Patients cannot have posterior fossa or intramedullary spine-only disease. Leptomeningeal disease is allowed anywhere in the neuroaxis. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.

‣ Resolution of AEs from any prior systemic anticancer therapy or radiotherapy to Grade 1 or baseline (except Grade 2 alopecia and Grade 2 sensory neuropathy)

‣ Medically able and willing to undergo placement of an Ommaya reservoir.

‣ Steroid dose anticipated to be ≤ 4 mg of dexamethasone a day or equivalent at time of first CAR-v3-TEAM-E infusion.

‣ Age ≥18 years

‣ Karnofsky ≥60% (see Appendix A).

‣ Must be able to undergo an MRI with contrast.

‣ Life expectancy of greater than 3 months.

‣ Participants must have adequate organ and marrow function as defined below:

⁃ absolute neutrophil count ≥1,000/mcL

• platelets ≥80,000/mcL

• total bilirubin ≤ institutional upper limit of normal (ULN)

• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN

• creatinine ≤ institutional ULN OR

• glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2

‣ For patients with Gilbert's syndrome, total bilirubin can be ≤ 3xULN.

⁃ Participant has no prior history of malignancy, unless the subject has been free of the disease for ≥5 years with the exception of the following noninvasive malignancies:

∙ Basal cell carcinoma of the skin

‣ Squamous cell carcinoma of the skin

‣ Carcinoma in situ of the cervix

‣ Carcinoma in situ of the breast

‣ Incidental histologic finding of prostate cancer (T1a or T1b) or prostate cancer that is curative

⁃ Left ventricular ejection fraction \>50% as determined by TTE.

⁃ The effects of CARv3-TEAM-E on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of CARv3-TEAM-E administration.

⁃ Ability to understand and the willingness to sign a written informed consent document.