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

Okada, H and Lieberman, FS and Walter, KA and Lunsford, LD and Kondziolka, DS and Bejjani, GK and Hamilton, RL and Torres-Trejo, A and Kalinski, P and Cai, Q and Mabold, JL and Edington, HD and Butterfield, LH and Whiteside, TL and Potter, DM and Schold, SC and Pollack, IF (2007) Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas. Journal of Translational Medicine, 5.

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Abstract

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 Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine.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 EphA 2883-891 . 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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Okada, H
Lieberman, FS
Walter, KA
Lunsford, LD
Kondziolka, DS
Bejjani, GK
Hamilton, RLhamil1@pitt.eduHAMIL1
Torres-Trejo, A
Kalinski, P
Cai, Q
Mabold, JL
Edington, HD
Butterfield, LHlhb3@pitt.eduLHB3
Whiteside, TL
Potter, DM
Schold, SC
Pollack, IFipollack@pitt.eduIPOLLACK
Date: 19 December 2007
Date Type: Publication
Journal or Publication Title: Journal of Translational Medicine
Volume: 5
DOI or Unique Handle: 10.1186/1479-5876-5-67
Schools and Programs: Graduate School of Public Health > Biostatistics
School of Medicine > Immunology
School of Medicine > Medicine
School of Medicine > Neurology
School of Medicine > Pathology
School of Medicine > Surgery
Refereed: Yes
Date Deposited: 17 Dec 2012 18:48
Last Modified: 13 Apr 2019 13:55
URI: http://d-scholarship.pitt.edu/id/eprint/16914

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