Inclusion Criteria
1. Age ≥ 18 years of age
2. Newly diagnosed Isocitrate dehydrogenase (IDH) wild type (CARIS result), MGMT promoter unmethylated (CARIS result) WHO grade IV glioma (e.g., glioblastoma (GBM) or high grade glioma with molecular features of GBM) with definitive resection prior to enrollment, and residual radiographic contrast enhancement on immediate post-surgical computed tomography (CT), or magnetic resonance imaging (MRI).
3. CMV positive or negative by IgG testing.
4. Karnofsky Performance Status (KPS) of \> 70%.
5. Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,000 cells/µl, platelets ≥ 100,000 cells/µl.
6. Serum creatinine ≤ 3 x the upper limit of normal (ULN), serum glutamic oxaloacetic transaminase (SGOT)≤ 3 times ULN
7. Bilirubin ≤ 1.5 times ULN (Exception: Patient has known Gilbert's Syndrome or patient has suspected Gilbert's Syndrome, for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)
8. Signed informed consent approved by the Institutional Review Board.
9. Female patients must not be pregnant or breast-feeding. Female patients of childbearing potential (defined as \< 2 years after last menstruation or not surgically sterile) must use a highly effective contraceptive method (allowed methods of birth control, \[i.e. with a failure rate of \< 1% per year\] are implants, injectables, combined oral contraceptives, intra-uterine device \[IUD; only hormonal\], sexual abstinence or vasectomized partner) during the trial and for a period of \> 6 months following the last administration of trial drug(s). Female patients with an intact uterus (unless amenorrhea for the last 24 months) must have a negative serum pregnancy test within 48 hours prior to first vaccination.
10. Fertile male patients must agree to use a highly effective contraceptive method (allowed methods of birth control \[i.e. with a failure rate of \< 1% per year\] include a female partner using implants, injectables, combined oral contraceptives, IUDs \[only hormonal\], sexual abstinence or prior vasectomy) during the trial and for a period of \> 6 months following the last administration of trial drug(s).
Exclusion Criteria
1. Patients with known potentially anaphylactic allergic reactions to gadolinium-diethylenetriaminepentaacetic acid (DTPA), or any component of the tetanus-diphtheria vaccine.
2. Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of multifocal disease, or leptomeningeal disease.
3. Areas of high-grade glioma outside the original radiation field on the post XRT/TMZ MRI.
4. Patients who cannot undergo MRI.
5. Severe, active comorbidity, including any of the following:
* Unstable angina and/or congestive heart failure requiring hospitalization;
* Transmural myocardial infarction within the last 6 months;
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of first -vaccination;
* Active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax \> 99.5°F/37.5°C)
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy;
* Known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
* Known immunosuppressive disease or Human Immunodeficiency Virus (HIV) and -Hepatitis C positive status;
* Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy;
* Active connective tissue disorders, such as lupus or scleroderma that, in the opinion of the treating physician, may put the patient at high risk for radiation toxicity.
6. Co-medication that may interfere with study results (e.g., immuno-suppressive agents other than corticosteroids).
7. Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin. (Treatment with tamoxifen or aromatase inhibitors or other hormonal therapy that may be indicated in prevention of prior cancer disease recurrence, are not considered current active treatment.)
8. Patients are not permitted to have had any other conventional therapeutic intervention other than surgery, steroids, and standard of care chemoradiation prior to enrollment.
9. Patients who received previous inguinal lymph node dissection or had radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies to treat a CNS tumor will be excluded.
10. Current, recent (within 4 weeks of the administration of this study agent), or planned participation in an experimental drug study.
11. Known history of autoimmune disease (with the exceptions of medically-controlled hypothyroidism and Diabetes Mellitus).
