Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas

Background: The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL)-4 gene transfected fibroblasts. Methods: In University of Pittsburgh Cancer Institute (UPCI) protocol 95-033, adult participants with recurrent glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) received gross total resection (GTR) of the recurrent tumors, followed by two vaccinations with autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK-transfected fibroblasts admixed with type-1 dendritic cells (DC) loaded with autologous tumor lysate. The participants were evaluated for occurrence of adverse events, immune response, and clinical response by radiological imaging. Results and Discussion: In UPCI 95-033, only 2 of 6 participants received the vaccinations. Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine. However, both participants who received two vaccinations demonstrated encouraging immunological and clinical responses. Biopsies from the local vaccine sites from one participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T cells. Interferon (IFN)-γ Enzyme-Linked Immuno-SPOT (ELISPOT) assay in another human leukocyte antigen (HLA)-A2+ participant demonstrated systemic T-cell responses against an HLA-A2-restricted glioma-associated antigen (GAA) epitope EphA2883-891. Moreover, both participants demonstrated clinical and radiological improvement with no evidence of allergic encephalitis, although both participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6 enrolled participants received scheduled vaccinations with no incidence of major adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment was well tolerated; however, we were unable to observe detectable IFN-γ post-vaccine responses or prolonged progression-free survival in these participants. Conclusion: Feasibility challenges inherent in the generation of a patient-specific gene transfection-based vaccine strongly suggests the need for more practical formulations that would allow for the timely administration of vaccines. Nevertheless, successful generation of type-1 DCs and preliminary safety in the current study provide a strong rationale for further efforts to develop novel glioma vaccines. © 2007 Okada et al; licensee BioMed Central Ltd

Hemangioblastoma of the posterior fossa: the role of multimodality treatment Hemangioblastoma da fossa posterior: papel do tratamento multimodal

The authors made a review of a series of patients with hemangioblastomas of the posterior fossa treated between 1973 and 1993. A total of 32 patients were analyzed with 24 patients receiving resection, 8 patients receiving radiosurgery and 2 patients receiving conventional radiotherapy. The mortality in the patients with a resection was considered acceptable with 2 deaths (8%) and with a morbidity of 3 patients (12.5%). A review of the literature suggests that conventional radiotherapy with high doses (45-60 Gy) may have a role in the post-operative control of hemangioblastomas and in some cases could be employed even before the resection in order to facilitate the surgery. The radiosurgical treatment is regarded like adjuvant. Poor results were obtained with radiosurgery in large tumors where low doses (less than 20 Gy) were used. Because of the rarity and complexity of these tumors, mainly when associated with von Hippel-Lindau disease, a multicenter study could be useful with the assessment of the optimal utilization and combination of these treatment modalities.Os autores fazem revisão de uma série de pacientes com hemangioblastomas da fossa posterior tratados entre 1973 e 1993: 32 pacientes foram analisados com 24 deles recebendo ressecção, 8 recebendo radiocirurgia e 2 recebendo radioterapia convencional. A mortalidade dos pacientes submetidos a ressecção foi considerada aceitável com 2 mortes (8%) c com morbidade de outros 3 pacientes (12,5%). A revisão de literatura sugere que a radioterapia convencional com altas doses (45-60 Gy) pode ter um papel no controle pós-operatório dos hemangioblastomas e em alguns casos pode ser empregada mesmo antes da ressecção com o objetivo de facilitar a cirurgia. O tratamento radiocirúrgico é considerado coadjuvante. Resultados ruins foram obtidos com a radiocirurgia em tumores grandes em que doses baixas (menos que 20 Gy) foram utilizadas. Devido a raridade e complexidade destes tumores, principalmente quando associados com a doença de von Hippel-Lindau, um estudo multicêntrico pode ser útil na avaliação da combinação e otimização dessas modalidades de tratamento

Introduction: the contribution of pathology to radiosurgery.

The term radiosurgery signifies any kind of application of ionizing radiation energy, in experimental biology or clinical medicine, aiming at the precise and complete destruction of chosen target structures containing healthy and/or pathological cells, without significant concomitant or late radiation damage to adjacent tissues. The goal of this study is to explore the short- and long-term pathophysiological effects of high-dose focused irradiation on neural tissue and its pathologies with histological, electron-microscopical tissue culture and biological-biochemical methods. Radiosurgical pathology focuses its scope and microscope on tissue, cellular, genetic and molecular changes in the human organism and experimental animals, or in cell lines and other in vitro experiments, generated by the ionizing radiation delivered from radiosurgical devices.Historical ArticleJournal Articleinfo:eu-repo/semantics/publishe

What can we learn from Pathology ?From the beginnings towards radiosurgical pathology

info:eu-repo/semantics/publishe