Inclusion Criteria:
* Must have magnetic resonance imaging (MRI) features consistent with and suspicious for malignant glioma. This will be Part A - Tissue (biopsy) and Rickham catheter placement.
* Must have histologically or cytologically confirmed glioblastoma multiforme prior to administration of the DRI γδ T cell injection. This will be Part B - Screening and Study Treatment.
* Prior therapy: Must have completed a standard temozolomide and radiotherapy treatment as described in Part A and be eligible to receive maintenance therapy with temozolomide (consistent with NCCN guidelines for newly diagnosed GBM and maintenance therapy).
* Age ≥18 yearsΦ: Because no dosing or adverse event data are currently available on the use of γδ T cells in patients \<18 years of age, children are excluded from this study but will be eligible for future pediatric Phase I single-agent trials.
* Karnofsky Performance Status ≥70%
* Life expectancy of greater than 12 weeks
* Patients must have organ and marrow function as defined below:
1. leukocytes \>3,000/µl
2. absolute neutrophil count \>1,500/µl
3. Hgb greater than or equal to 9.0 g/dL
4. platelets \>100,000/µl
5. total bilirubin within normal institutional limits
6. AST (SGOT)/ALT (SGPT) \<2.5 X institutional upper limit of normal
7. Normal electrolyte levels including sodium, calcium, potassium, chloride and magnesium
8. INR/PT/aPTT ≤1.5xULN
9. Normal EKG; if abnormal, NCS
10. Normal blood presure as adjusted for age
* Creatinine within normal institutional limits or if higher than the normal range, calculated creatinine clearance (CrCl) must be ≥ 50 mL/min/1.73 m2 (e.g., by Cockcroft-Gault formula); actual body weight must be used for CrCl unless body mass index (BMI) is \> 30 kg/m2, in which case, lean body weight must be used
Exclusion Criteria:
* Patients who have received any therapy for the treatment of GBM prior to inclusion in Part A and any treatment other than standard of care as described in Part A of this study including: cellular immunotherapy or gene therapy within 6 weeks prior to entering the study, surgical resection or alkylating agent chemotherapy within 4 weeks prior to entering the study, or have received experimental immunotherapy at any time, and those who have not recovered from adverse events due to therapeutic interventions administered more than 4 weeks earlier.
* Patients may not be receiving any other investigational agents.
* Contraindication to the placement of an intracranial access device (Rickham catheter) at the time of surgery.
* Prior history of encephalitis, multiple sclerosis, or other CNS infection
* Required steroid increase within 2 weeks of scheduled DRI γδ T cells administration.
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any othermedical condition that precludes surgery. Also, psychiatric illness/social situations that would limit compliance with study requirements.
* Allergies/hypersensitivity: Aminobisphosphonates such as Zoledronate®, Pamidronate® or similar
* Pregnant women are excluded from this study because the lentiviral- modified γδ T cells designed to express MGMT cells have an unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these cells, breastfeeding should be discontinued if the mother is treated with the lentiviral-modified γδ T cells designed to express MGMT. The following birth control methods are acceptable for this study in women of child- bearing potential:
* A Combination of TWO of the following:
1. Barrier method of contraception:
1. condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide
2. IUD
2. Hormone-based Contraceptive
* Note: Drug-drug interactions with some ARVs will make hormonal contraception a less reliable method.
* Because patients with immune deficiency will be unable to mount the anticipated immune response underlying this therapeutic rationale, HIV-seropositive patients are excluded from this study.
* Some of the contraceptive methods listed above may not prevent the spread of HIV to other people. Patients should discuss their contraceptive choices with their health care provider to choose the best way to both prevent pregnancy as required by this study and to prevent the spread of HIV to any partner(s).
* Patients with history of prior organ or bone marrow transplantation are not eligible.
