A maximum of 100 patients with resected, newly-diagnosed World Health Organization (WHO) Grade IV GBM will be enrolled in this study with the expectation that approximately 79 patients will be randomized to subsequent treatment after completion of radiation treatment with concurrent temozolomide. Effective March 2017, randomization to Group III has been terminated. All consented patients will undergo a leukapheresis after resection for harvest of Peripheral Blood Lymphocytes (PBLs) for generation of DCs. Patients will then receive Radiation Therapy (RT) and concurrent TMZ at a standard targeted dose of 75 mg/m\^2/d. Patients should start RT within approximately 6 weeks of surgery. Patients who experience progressive disease during radiation, are dependent on steroid supplements above physiologic levels at time of first vaccination, are unable to tolerate TMZ, or whose DCs or PBLs fail to meet release criteria will be withdrawn from the study and replaced and will not undergo repeat leukapheresis. For patients whose initial leukapheresis yields less than 3 vaccines, repeat leukapheresis may be obtained a minimum of 2 weeks from the previous leukapheresis (and may be repeated as needed) if pre-pheresis blood work is within the Apheresis Center's parameters and as long as this does not cause a significant delay in treatment for the patient.

After RT and concurrent TMZ, patients will then be randomized and begin the initial cycle of TMZ at a standard targeted dose of 150-200mg/m\^2/d for 5 days at the discretion of the treating oncologist 4 (± 2) weeks after completing RT. The study cycle of TMZ comprises a targeted dose of 150-200mg/m\^2/d for 5 days every 5 (± 1) weeks. All patients will receive up to a total of 10 DC vaccines given bilaterally at the groin site unless progression occurs. DC vaccines will be given intradermally (i.d.) and divided equally to both inguinal regions. DC vaccines #1-3 will be given every two weeks, thus delaying the initiation of TMZ cycle 2. Patients will then be vaccinated in conjunction with subsequent TMZ cycles every 5 (± 1) weeks for a total of 6 to 12 cycles after RT at the discretion of the treating oncologist. DCs will be given on day 21 ± 2 days of each TMZ cycle. DC vaccinations will continue during TMZ cycles up to a total of 10 unless progression occurs.

Before the first DC vaccination, all patients will receive immunization with 0.5 mL of Td intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Those assigned to Group III will receive basiliximab 20 mg infusions 1 week before the 1st and 1 week before the 2nd vaccine. At the time of the fourth DC vaccine, patients will receive pre-conditioning per the assigned group (Group I-unpulsed DCs i.d.; Group II- Td i.d.; Group III-Td i.d.). A single dose of Td toxoid (1 flocculation unit, in 0.3 milliliters (mLs) of saline for a total volume of 0.4 mLs) or 0.4 mLs of 1 x 10\^6 autologous unpulsed DCs in saline will be administered to a single side of the groin, and 0.4 mLs of saline administered to the contralateral side 12-24 hours prior to the fourth DC vaccine, which is always given bilaterally at the groin site. Patients in Groups I and II will then receive 111In-labeled DCs to compare the effects of different skin preparations on DC migration followed by Single-Photon Emission Computed Tomography and Computed Tomography (SPECT/CT) imaging immediately and at 1 and 2 days after injection. Group III will not undergo migration studies. Groups I and II will be double blinded. Group III will not be blinded.

All patients will undergo leukapheresis again for immunologic monitoring with specific assessment of baseline antigen-specific cellular and humoral immune responses and further DC generations 4 (± 2) weeks after vaccine #3. Patients will be imaged bimonthly without receiving any other prescribed anti-tumor therapy. Patients will undergo an additional leukapheresis for generation of DCs if needed to continue vaccinations.

As part of standard care for these patients, upon tumor progression, participants may undergo stereotactic biopsy or resection. As this is not a research procedure consent will be obtained separately. However, if tissue is obtained, it will be used to confirm tumor progression histologically and to assess immunologic cell infiltration and pp65 antigen escape at the tumor site.