The major objective of this study is to develop laboratory tests of clinical immunotherapy for patients with malignant glioma. The clinical trial involves: 1)Harvesting of the patient's own lymphocytes. 2)Their activation by means of phytohemagglutinin (PHA)/interleukin-2 (IL-2), in vitro culture. De-bulking of the tumor during craniotomy. 4) Implantation of fully activated lymphocytes, together with IL-2, into the tumor bed. The laboratory tests use 31P magnetic resonance spectroscopy (MRS) (and later 1H water suppressed MRS), to assay key metabolites of IL-2 activated lymphocytes. Activated human lymphocytes have a characteristics metabolism which can be monitored in a non-invasive assay by means of 31P MRS. The same assay distinguishes a target tumor cell line (K562) from lymphocytes, and demonstrates reproducible changes when that target cell is """"""""killed"""""""". Lymphocytes harvested from the patient will be assayed by MRS to determine resting metabolism, the degree of activation achieved with PHA/IL-2, and the capacity to kill K562. Each assay will be evaluated as a predictor of clinical outcome. The patient's glioma cells in culture will then be substituted for K562, as the correct taRGET FOR LYMPHOCYTE KILLING. By studying 20 patients, we will establish the predictive value of MRS. The effects of introducing the correct target cell will be documented in a further 20 patients. A major development in clinical magnetic resonance spectroscopy is the ability to directly monitor the metabolism of brain tumors in patients. This new generation of laboratory tests may lead to non-invasive assays of clinical immunotherapy.
