Cellular Adoptive Immunotherapy Using Genetically Modified T-Lymphocytes in Treating Patients With Recurrent or Refractory High-Grade Malignant Glioma

RATIONALE: Cellular adoptive immunotherapy may stimulate the immune system in different ways and stop cancer cells from growing.

PURPOSE: This clinical trial is studying the side effects of cellular adoptive immunotherapy using genetically modified T-lymphocytes and to see how well it works in treating patients with recurrent or refractory high-grade malignant glioma.

OBJECTIVES:

Primary

* To assess the feasibility and safety of cellular immunotherapy utilizing ex vivo expanded autologous CD8-positive T-cell clones genetically modified to express the IL-13 zetakine chimeric immunoreceptor and the Hy/TK selection/suicide fusion protein in patients with recurrent or refractory, high-grade malignant glioma.

Secondary

* To evaluate the antitumor activity of adoptively transferred clones in these patients.
* To screen for the development of anti-IL13 zetakine and anti-HyTK immune responses in these patients.
* To evaluate the efficacy of ganciclovir administration for ablating transferred clones in vivo should toxicity be encountered.

OUTLINE:

* Leukapheresis and therapy preparation: Patients undergo leukapheresis to obtain peripheral blood mononuclear cells. T-cells isolated from the peripheral blood are then genetically modified, hygromycin-resistant cloned, expanded ex vivo, and cryopreserved until the first clinical or radiographic evidence of recurrence or progression. Patients with documented disease recurrence or progression undergo re-biopsy or re-resection of the tumor and placement of a reservoir-access device (Rickham shunt) into the tumor resection cavity prior to autologous T-cell clone infusion therapy.
* Autologous T-cell clone infusion: Patients receive an infusion of autologous antigen-specific CD8+ cytotoxic T-lymphocyte clones over 5-10 minutes on days 1, 3, and 5 of weeks 1 and 2. Treatment repeats every 3 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving tumor regression with residual disease by MRI after 4 courses of study therapy may receive up to 2 additional courses in the absence of disease progression, unacceptable toxicity, or a complete response.

Patients undergo blood, cerebrospinal fluid, and tissue sample collection periodically for correlative studies. Samples are assessed for IL13Rα2 expression levels, susceptibility to redirected T-cell effector mechanisms, and other tumor and T-cell activation markers.

After completion of study treatment, patients will be followed monthly for 3 months, then every 3 months for two years, and then annually for at least 15 years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed malignant glioma at original diagnosis

  * Grade III or IV disease
  * Refractory or recurrent disease
  * Unifocal site of original disease in cerebral cortex
* No clinical evidence of progressive encephalopathy
* Has not undergone recent re-resection of recurrent or progressive disease
* No communication between the tumor resection cavity and the ventricles and deep cerebrospinal fluid pathways as documented by post-operative MRI scan

PATIENT CHARACTERISTICS:

* Karnofsky performance status 70-100%
* Life expectancy \> 3 months
* WBC ≥ 2,000/dL
* ANC \> 1,000/dL
* Platelet count ≥ 100,000/dL (unsupported by transfusion or growth factor)
* Creatinine \< 1.6 mg/dL
* Bilirubin \< 1.5
* SGOT and SGPT \< 2 times upper limit of normal
* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception
* Able to understand protocol basic elements and/or risks/benefits of participating in this pilot study
* No requirement for supplemental oxygen to keep saturation \> 95% that is not expected to resolve within 2 weeks
* No uncontrolled cardiac arrhythmia
* No hypotension requiring pressor support
* No renal dialysis dependency
* No refractory seizure disorder
* No concurrent non-malignant illness that is poorly controlled with treatment or is of such severity the investigators deem it unwise to enter the patient on protocol
* No severe infection for which patient is being treated
* No history of ganciclovir and/or Prohance contrast allergy or intolerance
* No HIV positivity within the past 3 months

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Must have recovered from major surgery
* At least 4 weeks since primary therapy and no steroid dependence
* At least 2 weeks since prior adjuvant cytotoxic chemotherapy and recovered
* No concurrent systemic corticosteroids, except for use in managing T-cell therapy toxicity
* No concurrent immunotherapy (i.e., interferons, vaccines, or other cellular products)
* No concurrent pentoxifylline
* No other concurrent investigative agents
* No concurrent ganciclovir or ganciclovir derivative
* No concurrent acyclovir for non-life threatening herpes virus infection