Six CMV seropositive patients with newly-diagnosed GBM will be randomized to receive CMV-ALT (3 x 107/Kg) with or without vaccine with CMV-DCs (2 x 107). All patients will undergo a leukapheresis after resection for harvest of PBLs for CMV-ALT and CMV-DC generation. Patients will then receive RT and concurrent TMZ at a standard targeted dose of 75 mg/m2/d. Patients with histologically or clinically-proven progressive disease during radiation, dependent on steroid supplements above physiologic levels at time of vaccination, and are unable to tolerate TMZ will be replaced. If sufficient CMV-specific T-cells can't be expanded or ALT doesn't meet release criteria, the patient will be replaced and their cells may be used to offer them another DC vaccination study, such as ATTAC Pro00003877. Remaining patients will then receive the initial cycle of TMZ at a standard targeted dose of 200mg/m2/d for 5 days 3 + 1 weeks after completing RT and will be randomized to receive CMV-DCs or saline simultaneous with CMV-ALT as vaccine #1. While the standard targeted dose of 200mg/m2/d for 5 days TMZ treatment is recommended, TMZ regimen may be adjusted at the discretion of the treating neuro-oncologist. Patients with MRI changes consistent with pseudoprogression who continue on TMZ will receive CMV-ALT with vaccinations as scheduled. Peripheral blood will be drawn at 0 hours, 24 hours, 48 hours, 72 hours, and 1 week post vaccine #1 for T-cell kinetics. DCs or saline will be given intradermally and divided equally to both inguinal regions. Vaccines #2 and #3 will occur at 2 week intervals. All patients will then undergo leukapheresis again for immunologic monitoring with specific assessment of baseline antigen-specific cellular and humoral immune responses.

If the initial dose of CMV-ALT is safe and the combination of CMV-DCs is safe and does not produce an inferior CMV pp65-specific immune response, a 3rd cohort of patients will be enrolled and receive a higher dose of CMV-ALT (3 x 108/Kg) along with vaccine with CMV-DCs (2 x 107). If the combination is unsafe or inferior only the CMV-ALT will be given. If CMV-ALT (3 x 108/Kg) is safe a 4th cohort of 3 patients will be enrolled and receive the same treatment as the 3rd cohort except the T-cells will be labeled with 111In and cultured ex vivo with 13C-glucose and their proliferation, persistence, and migration followed by peripheral blood sampling, Single Photon Emission Computed Tomography (SPECT ), and MRI.

After the initial 3 vaccines, patients will then receive subsequent TMZ cycles every 4 weeks for at least 6 cycles and up to 12 cycles after RT. TMZ will be given on days 1-5 of a 28 day cycle. Patients will then be imaged bimonthly and followed until death. This study will be halted if any 2 patients in any cohort of 3 experience a drug-related Grade IV or irreversible Grade III toxicity.

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. Patients consenting to biopsy or resection will also be offered intratumoral vaccination with CMVpp65 LAMP-loaded, 111In-labeled DCs at the time of surgery to determine if they migrate to cervical lymph nodes.