ABSTRACT
Nineteen patients with recurrent high grade gliomas were treated in a phase I/II trial with aggressive debulking of the tumor, mitogen activated IL-2 stimulated peripheral blood lymphocytes (MAK cells), and rIL-2. Phytohemagglutin (PHA) was introduced into the tumor site in 16 patients prior to implanting MAK cells and IL-2 in an attempt to trigger more effective lysis of the tumor in vivo. In vitro both TNF bioactivity and cytolytic activity of long term cultured MAK (LMAK) cells were dramatically enhanced by adding PHA to the cultures of these activated PBL. Three of eleven patients (27%) had a decrease in size of the enhancing lesion on CT and/or MRI. Seven (37%) patients clinically improved. Median survival after therapy was 30 weeks. PHA was shown to be safe in vivo and more effective than IL-2 triggering enhanced effector function in vitro.
Subject(s)
Brain Neoplasms/therapy , Glioma/therapy , Immunotherapy/methods , Killer Cells, Lymphokine-Activated/immunology , Neoplasm Recurrence, Local/therapy , Phytohemagglutinins/therapeutic use , Adrenal Cortex Hormones/pharmacology , Adult , Aged , Brain Neoplasms/pathology , Combined Modality Therapy , Cytokines/biosynthesis , Cytotoxicity, Immunologic , Female , Glioma/pathology , Humans , Immunotherapy/adverse effects , Interleukin-2/pharmacology , Killer Cells, Lymphokine-Activated/drug effects , Male , Middle Aged , Mitogens/pharmacology , Neoplasm Recurrence, Local/pathology , Treatment OutcomeABSTRACT
Seven patients with recurrent high-grade glioma were treated in a Phase I/II trial with surgical debulking, after which mitogen-activated IL-2-stimulated killer (MAK) lymphocytes and 10(5) units rIL-2 were implanted in the surgical defect. The therapy was well tolerated, and the mean survival of this group of patients was 29 weeks. Tumor necrosis factor (TNF) production by MAK lymphocytes stimulated with IL-2 in vitro was measured. A significant (r = .78, p = .04) correlation between survival of patients after therapy and the ability of the MAK lymphocytes to produce TNF in vitro was noted. A significant negative correlation (r = -.82, p = .02) was found when comparing TNF production and increasing tumor size measured on MRI. No correlation was found between TNF production in vitro and MAK lymphocytes lytic activity on K562 and U373 target cells. No correlation was found between survival and MAK cell lytic activity measured on K562 and U373 target cells. We conclude that TNF production in vitro and cytotoxic activity measured in vitro are measures of different antitumor activity in vivo and in vitro. TNF production during IL-2-stimulated proliferation may be an important in vitro assay in terms of predicting length of survival of recurrent high-grade gliomas.
Subject(s)
Glioma/therapy , Interleukin-2/therapeutic use , Killer Cells, Lymphokine-Activated/transplantation , Neoplasm Recurrence, Local/therapy , Phytohemagglutinins/pharmacology , Tumor Necrosis Factor-alpha/biosynthesis , Adult , Chromium Radioisotopes , Combined Modality Therapy , Enzyme-Linked Immunosorbent Assay , Female , Glioma/mortality , Humans , Immunotherapy/methods , Killer Cells, Lymphokine-Activated/drug effects , Killer Cells, Lymphokine-Activated/metabolism , Male , Neoplasm Recurrence, Local/mortality , Recombinant Proteins/therapeutic use , Survival Rate , Transplantation, AutologousABSTRACT
A 38-year-old Caucasian male died following complications of a myocardial infarct. He had been obese and reportedly hyperphagic. At autopsy an 8-cm-in-diameter suprasellar epidermoid cyst was discovered to have destroyed much of his frontal lobe tissue. The histogenesis and classification of this large, clinically unsuspected lesion are discussed.
