Inclusion Criteria:

Pre-surgery tissue acquisition Inclusion criteria

1. >18 years old
2. Life expectancy of greater than 12 weeks.
3. Able to read and understand the informed consent document; must sign the informed consent
4. Must have suspected diagnosis of Glioblastoma Multiforme with a surgical intent to resect at least 90% of enhancing disease
5. Must be eligible for post-surgical treatment with radiotherapy and temozolomide

Post-radiation therapy/pre-vaccine eligibility Inclusion criteria

1. Agree to use contraception or abstain from sexual activity from the time of consent through 1 month after the end of study drug administration
2. Negative serum pregnancy test for female patients of childbearing potential
3. Patients with histologically proven, non-progressive glioblastoma multiforme (GBM)
4. Patient must have received standard of care radiation and temozolomide therapy
5. Must have undergone a > 90% resection (determined by the PI) measured by postoperative magnetic resonance imaging (MRI) scan, T1-weighted contrast scan, or CT scan if clinically indicated, performed within 48 hours after surgery
6. All radiotherapy must be discontinued at least 2 weeks and no more than 5 weeks prior to the first planned vaccine administration
7. Availability of >4 doses of vaccine (>4 vials for clinical administration produced from the tumor provided)
8. Karnofsky functional status rating >70
9. Adequate bone marrow function (ANC > 1,500/ mm3; platelet count >100,000/mm3), adequate liver function (serum glutamic oxaloacetic transaminase/ aspartate aminotransferase [AST] and alkaline phosphatase <2.5 times institutional upper limit of normals [IULNs] and bilirubin (total) <1.5 mg*IULN), and adequate renal function (BUN and creatinine <1.5 times IULNs)

Exclusion Criteria:

Pre-surgery tissue acquisition

1. Current diagnosis of Human Immunodeficiency Virus (HIV testing is not required per protocol)
2. Any prior diagnosis of any other cancer or other concurrent malignancy, with the exception of adequately treated nonmetastatic in situ carcinoma of the uterine cervix or nonmetastatic nonmelanoma skin cancer unless in complete remission and off all therapy for that disease for a minimum of 5 years
3. Any systemic autoimmune disease (e.g., Hashimoto's thyroiditis) and/or any history of primary or secondary immunodeficiency
4. Prior history of HSPPC-96 use or immunotherapy for glioma
5. Planned use or current use of other investigational therapy for the treatment of glioma

Post-radiation therapy/pre-vaccine Exclusion

1. Inability to comply with study-related procedures
2. Prior diagnosis of any other cancer or other concurrent malignancy, with the exception of adequately treated nonmetastatic in situ carcinoma of the uterine cervix or nonmetastatic nonmelanoma skin cancer unless in complete remission and off all therapy for that disease for a minimum of 5 years
3. Current or active use of chemotherapy (except temozolomide) or immune therapy
4. Contrast MRI findings (or CT scan if clinically indicated) consistent with >10% increase in contrast enhancement interpreted (from the post-surgery scan) to be tumor progression prior to vaccination as determined by the PI
5. Patients with active uncontrolled infection
6. Evidence of bleeding diathesis
7. Unstable or severe intercurrent medical conditions
8. Female patients who are pregnant or breastfeeding