title: T cell adoptive immunotherapy of newly diagnosed gliomas.
abstract: Patients with newly diagnosed gliomas were treated with adoptive transfer of ex vivo activated T lymphocytes, derived from lymph nodes (LNs) draining autologous tumor vaccines, to determine the long-term toxicity of this treatment. Twelve consecutive patients were enrolled: 2 with grade II astrocytoma, 4 with anaplastic gliomas, and 6 with glioblastoma multiforme. Patients were injected intradermally with short-term cultured autologous irradiated tumor cells, admixed with granulocyte macrophage colony-stimulating factor, to stimulate draining LNs. The LN cells were activated with staphylococcal enterotoxin A for 48 h and then cultured in medium containing interleukin 2 for an additional 6-8 days and subsequently transferred i.v. to the patients. The number of cells obtained from the LNs ranged from 9 x 10(7) to 1.1 x 10(9), and the median cell proliferation was 41-fold. The dose of T cells infused ranged from 0.6 to 5.5 x 10(10) with a median of 1.1 x 10(10), the majority of which were CD 4+ (mean, 71%). The entire treatment was performed as outpatient therapy and was associated with a toxicity of grade 2 or less, consisting mainly of fever, nausea, and myalgias during the first 24 h. There were no indications of late adverse events from this treatment even among three patients with follow-up greater than 2 years post T cell transfer. Moreover, four patients demonstrated partial regression of residual tumor. This Phase I clinical trial of adoptive immunotherapy for patients with newly diagnosed malignant gliomas demonstrates feasibility, lack of long-term toxicity, and several objective clinical responses.
authors.affiliation: Center for Surgery Research, The Cleveland Clinic Foundation, Ohio 44195, USA. plautzg@ccf.org
authors.forename: G E
authors.initials: GE
authors.lastname: Plautz
authors.forename: D W
authors.initials: DW
authors.lastname: Miller
authors.forename: G H
authors.initials: GH
authors.lastname: Barnett
authors.forename: G H
authors.initials: GH
authors.lastname: Stevens
authors.forename: S
authors.initials: S
authors.lastname: Maffett
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: P A
authors.initials: PA
authors.lastname: Cohen
authors.forename: S
authors.initials: S
authors.lastname: Shu
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001254:Astrocytoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015704:CD4 Antigens / Q000276:immunology; D019496:Cancer Vaccines; D003520:Cyclophosphamide / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004768:Enterotoxins / Q000494:pharmacology; D004806:Ependymoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D005909:Glioblastoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015704:CD4 Antigens; D019496:Cancer Vaccines; D004768:Enterotoxins; D007376:Interleukin-2; C026066:enterotoxin A, Staphylococcal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D066246:ErbB Receptors