Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of recurrent glioblastoma: preliminary observations in a patient with a favorable response to therapy

Okada, Hideho; Lieberman, Frank S.; Edington, Howard; Witham, Timothy F.; Wargo, Mark J.; Cai, Quan; Elder, Elaine; Whiteside, Theresa L.; Schold, S. Clifford; Pollack, Ian F.

doi:10.1007/bf02700016

Cited by 59 publications

(53 citation statements)

References 25 publications

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“…In recent years, we have examined the applicability of a series of tumor cellbased immunization approaches for patients with gliomas [9][10][11][12][13][14][15]. Although promising results have been achieved [9,16,17], a limitation of this strategy is the need for autologous tumor and the time delay involved in generating a patient-specific vaccine. In contrast, vaccines in the form of synthetic peptides encoding T-cell epitopes in GAA would eliminate the need for autologous fresh glioma explants to generate clinical grade vaccines, facilitate timely vaccine production, and potentially reduce the risk of autoimmune encephalitis.…”

Section: Introductionmentioning

confidence: 99%

Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas

et al. 2008

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We investigated the protein expression of three glioma-associated antigens (GAAs) in pediatric brain stem glioma (BSG) and non-brain stem glioma (NBSG) cases with a view to their possible use in immunotherapy. Expression of EphA2, IL-13Rα2 and Survivin were studied by immunohistochemistry on paraffin-embedded tissues using a series of 15 BSG cases and 12 NBSG cases. Thirteen of 15 BSGs and all 12 NBSGs expressed at least one of GAAs; and 7 BSGs and 9 NBSGs expressed at least two of these GAAs at higher levels than non-neoplastic brain. There was no association between the tumor grade and levels of GAA expression. Although many cases demonstrated diffuse expression of GAAs throughout specimens, partial or patchy expression was noted in a small number of cases, suggesting a need for targeting multiple GAAs in immunotherapy. These results suggest that EphA2, IL-13Ralpha2 and Survivin are suitable targets for developing vaccine strategies for pediatric glioma.

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Section: Introductionmentioning

confidence: 99%

Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas

et al. 2008

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“…Okada et al, described a case where IL-4 was used in treatment of recurrent GBM [45]. The IL-4 transgene was expressed by transfected fibroblasts.…”

Section: Cytokinesmentioning

confidence: 99%

“…Follow up by MRI showed regression not only of the injected mass, but also of the temporal lesion. Unfortunately, the patient showed tumor relapse and died 13 months after the therapy.Okada et al, described a case where IL-4 was used in treatment of recurrent GBM [45]. The IL-4 transgene was expressed by transfected fibroblasts.…”

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confidence: 99%

Current Immunotherapeutic Strategies for Central Nervous System Tumors

Kushen¹,

Sonabend²,

Lesniak³

2007

Surgical Oncology Clinics of North America

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Immunotherapy has emerged as a promising tool in the management of malignant central nervous system (CNS) tumors. Despite the improvement in patient survival, traditional approaches -which consist mostly of surgery, radiotherapy, and chemotherapy -have been largely unsuccessful in permanently controlling these aggressive tumors. Immunotherapeutic strategies therefore offer not only a novel approach, but also an advantage in a way other modalities have been failing. Specifically, the capabilities of the immune system to recognize altered cells while leaving normal cells intact offer tremendous advantage over the conventional therapeutic approaches. This review summarizes our current understanding of immunotherapeutic treatment modalities employed in clinical trials for management of malignant CNS tumors. Keywordsclinical trials; glioma; glioblastoma; immunotherapy; dendritic cells; cytokines; toxins Immune system and the CNSThe immune system has the ability to recognize and destroy foreign cells via two separate modalities: innate and adaptive immunity. The innate component consists of macrophages, natural killer (NK) cells, monocytes, and granulocytes. These cells identify molecular patterns involved in cellular transformation and release various cytokines and inflammatory mediators. The innate response lacks the memory capability for foreign antigens, a feature present in adaptive immune response. This latter component of immune system also features specificity for foreign antigens, imparted by presence of receptors on lymphocytes. Antigen presenting cells (APCs) also play a role in the adaptive response -they engulf foreign antigens and present them to the lymphocytes in the context of major histocompatibility complex. CD4+ T cells Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Recent advances in research on antigen presentation, specific cytokines, and T-cell cytotoxicity have given new direction to immunotherapeutic strategies against CNS tumors. Evidence of CNS manifestations after peripheral vaccination with brain-specific antigens in EAE and paraneoplastic cerebellar degeneration models have also lead to a search for possible immunotherapy regimens for management of malignant gliomas [32]. Current directions in immunotherapy investigations include the use of various cytokines, dendritic cells, viral and peptide vaccines, and toxins. NIH Public Access CytokinesCytokines augment T cell activation and MHC antigen expression. Antitumor effects mediated by expression of cytokines in cancer models have been demonstrated with IL-2, IL-4, IL-12, IL-23, IFN-α, and ...

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“…4 Recently, various DC-based therapies have been tried to elicit antitumor responses, 6,[8][9][10][11][12][13][14][15] and DCs have been used for therapy in patients with some malignant tumors such as malignant melanoma, lymphoma, renal cell carcinoma, pancreatic, and gastric cancer. 16 Interferon (IFN)-a has been used to treat patients with not only viral infections such as hepatitis B and C but also some malignant tumors such as melanoma, renal cell carcinoma, and leukemia. The effects of type I IFN include antiviral function, enhancement of IFN-a/b production, 17,18 and inhibition of cell growth and angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Dendritic cell therapy with interferon-α synergistically suppresses outgrowth of established tumors in a murine colorectal cancer model

et al. 2005

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Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of recurrent glioblastoma: preliminary observations in a patient with a favorable response to therapy

Cited by 59 publications

References 25 publications

Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas

Expression of glioma-associated antigens in pediatric brain stem and non-brain stem gliomas

Current Immunotherapeutic Strategies for Central Nervous System Tumors

Dendritic cell therapy with interferon-α synergistically suppresses outgrowth of established tumors in a murine colorectal cancer model

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