This is a phase 1 study for patients with newly diagnosed MGMT unmethylated IDH wild-type glioblastoma utilizing autologous activated T-cells armed with bispecific antibody (EGFR-BATs) that recognize the tumor. The investigators hypothesized that the combination of infusions of EGFR BATs and low-intensity focused ultrasound would induce blood-brain barrier opening and increase the permeability of the adoptive immunotherapy. The investigators will radiolabel the EGFR BATs with 89Zr-oxine for subsequent PET imaging to determine the trafficking and uptake of this approach. There is a concern that several infusions of EGFR BATs before BBB opening could change the immune tumor microenvironment that would not allow a permissive BBB after LIFU. Therefore, Arm A will have two LIFU with BBB opening after the 4th and the 8th infusion, and Arm B will have three LIFU with BBB opening after the 1st, 4th, and 8th infusions. This study will determine the safety and feasibility of the combination of low-intensity focused ultrasound (LIFU) with microbubbles BBB opening and EGFR BATs and the access of the adoptive cell immunotherapy to the tumor microenvironment to inform future studies.

Inclusion Criteria:

1. Newly diagnosed supratentorial glioblastoma or gliosarcoma IDH wildtype and MGMT unmethylated that express EGFR (score ≥ 1 by IHC)) and confirmed by UVA pathology review.
2. Age ≥ 18 and ≤ 70 years at the time of signing informed consent.
3. Karnofsky Performance Status (KPS) ≥ 70.
4. Be willing and able to provide written informed consent for the trial.
5. Females of childbearing potential, and males, must be willing to use an effective method of contraception.
6. Maximal surgical debulking of the tumor was performed where residual contrast enhancement is 2 cm3 or less on immediate post-operative MRI. Intraoperative post-resection MRI is acceptable.
7. Able to communicate during the LIFU BBB opening procedure.
8. BBB opening target(s) must lie in non-eloquent area(s).
9. The brain tumor to be treated must be in the treatment envelope of the NaviFUS system with a minimum distance of 30 mm from the inner skull table.
10. Females of childbearing potential should have a negative serum pregnancy test. Males who are partners of females of childbearing potential must agree to use an acceptable method of contraception throughout the study and for 1 month following completion of the EGFR BATs infusions.
11. Demonstrate adequate organ function as defined in Table 1. All screening labs should be performed within 10 days before leukapheresis.

Exclusion Criteria:

1. Patients with a diagnosis of another malignancy within 2 years of being on-study. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or any type of in situ cancer. Patients must not be on any treatment for another malignancy.

2. Patients undergoing only biopsy (partial resection or greater is required).

3. Patients with cerebellar or brainstem tumors.

4. Patients with evidence of leptomeningeal dissemination or subependymal spread on initial MRI.

5. Patients with extracranial metastases.

6. Patients with evidence of acute intracranial hemorrhage.

7. Known hypersensitivity to cetuximab or another EGFR antibody.

8. Known sensitivity to gadolinium-based contrast agents.

9. Known sensitivity to Lumason® ultrasound contrast agent.

10. Alpha 1,3 Galactose IgE ("alpha gal") test result outside of the reference range (indicating likely hypersensitivity to cetuximab).

11. Patients with claustrophobia.

12. Clips, shunts, or other non-MRI compatible metallic implanted objects in the skull or the brain.

13. Evidence of active bleeding or bleeding diathesis.

14. Unable to discontinue use of anticoagulant therapy as per local standard.

15. Scalp atrophy or scars in the expected location of the ultrasound transducer.

16. Cardiac Status: Patients will be ineligible for treatment on this protocol if (before protocol entry):

    • There is a history of a recent (within one year) myocardial infarction or stroke.
    • There is a current or prior history of angina/coronary symptoms requiring medications and/or a history of depressed left ventricular function (LVEF < 45%).
    • Patient has a pacemaker.

17. There is clinical evidence of congestive heart failure requiring medical management.

18. Has Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

19. Has received a live vaccine within 30 days of leukapheresis.

20. Has received any treatment for GBM besides surgery.

21. Females must not be pregnant or breastfeeding.

22. Ongoing immunosuppressive therapy except for corticosteroids

23. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

24. A patient may be excluded if, in the opinion of the treating investigator, the patient is not capable of being compliant.