Imiquimod/Brain Tumor Initiating Cell (BTIC) Vaccine in Brain Stem Glioma

Vaccine will be produced by the University Of Minnesota Molecular and Cellular Therapeutics
Facility using the established brain tumor initiating cell (BTIC) cell line GBM-6 as the
antigen source. Vaccine administration will begin at four weeks (week 10) following
completion of radiation therapy and will be given every two weeks for four doses. At the time
of the 1st and 3rd vaccinations, additional 180 cGy fractions will be delivered in single
doses in a novel effort to induce NKG2D ligand upregulation (thereby "sensitizing" residual
tumor to lymphocyte attack). The total radiation dose for each patient will be 5940 cGy.
Subsequent vaccinations will be given every four weeks and will continue to a maximum of one
year from study enrollment, by which time median survival will have passed based on
historical data. Imaging will be obtained at study entry (post radiation therapy) and every
eight weeks thereafter to eighteen months, after which time the interval between imaging
follow-up episodes will be determined by the patient's clinical status. Imaging will include
MRI of the brain using our current institutional brain tumor imaging protocol. Imaging will
also include SPECT/MRI and perfusion MRI. FDG-PET imaging may be used in certain cases to
differentiate tumor necrosis from progression.

Inclusion Criteria

- Age 16 years or older patients with histologically confirmed glioblastoma multiforme
(GBM) World Health Organization (WHO) grade III-IV with recurrent or progressive
disease after standard therapy (enrollment plan 1).

- Age 3 years and older patients with diffuse intrinsic pontine glioma (DIPG) diagnosed
by magnetic resonance imaging (MRI). Completion of standard radiation therapy (not to
exceed 5580 cGy) with a post radiation therapy (RT) MRI that shows no disease
progression when compared with pre-RT MRI. All patients must be treated with Intensity
Modulated Radiation Therapy (IMRT) or an equivalent conformal technique. Patients from
an outside institution who are referred after the start of radiation therapy may
complete initial radiation therapy at their home institution as long as dosage
guidelines are met and the total dose does not exceed 5580 cGy at the time of study
registration (enrollment plan 2 and 3).

- all patients regardless of diagnosis must be clinically stable and off or on low dose
(no more than 0.1 mg/kg/day, maximum of 4 mg/day dexamethasone) corticosteroid for at
least 1 week prior to study enrollment.

Exclusion Criteria:

- Pregnant or breast-feeding. Pregnancy testing will be performed on all menstruating
females within 14 days prior to study enrollment.

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or
psychiatric illness/social situations that would limit compliance with study
requirements

- Currently receiving any chemotherapy, investigational agents or registration on
another therapy based trial or received chemotherapy with radiation therapy

- History of immune system abnormalities such as hyperimmunity (e.g., autoimmune
diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS,
ongoing pregnancy, transplant immunosuppression)

- Any isolated laboratory abnormality suggestive of a serious autoimmune disease

- Any conditions that could potentially alter immune function (AIDS, multiple sclerosis,
diabetes, renal failure)

- Receiving ongoing treatment with immunosuppressive drugs, excluding those patients
requiring dexamethasone for treatment of tumor-related edema