Inclusion Criteria:  Subjects with newly diagnosed typical or non-typical, biopsy-proven DIPG or DMG are eligible for study enrollment. Biopsy is not required for subjects with radiographically typical DIPG meeting imaging criteria. Biopsy is required for DMG's and non-radiographically typical DIPG. Histone mutation must be confirmed by pathology report. Radiographically typical DIPG defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons.  = Subjects ages > or = to 12 months and < or = 18 years ("Lead In", Part A, and Part B require first three patients be > or = to 12 years of age)  BSA > or = 0.35m2 at the time of study enrollment Performance score: Karnofsky >50% of subjects >16 years of age and Lansky > or = 50 for subjects < or = 16 years of age. Subjects who are unable to walk because of paralysis but are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score. Must start radiation therapy within 42 days from date of diagnostic imaging. C1D1 must be within 42 days to 70 days post radiation (6-10 weeks). Patients CANNOT receive temozolomide during radiation Corticosteroids should be weaned as tolerated after radiation therapy with the goal of < or = 0.5mg/kg/day for a minimum of 7 days prior to enrollment. Subjects must have measurable disease  Exclusion Criteria:  Patients cannot receive temozolomide during radiation Disseminated disease Subjects who have received any cancer therapy except for radiation Autoimmune or immune disorders Active respiratory disorder or infection Active viral infection