Cytokine gene therapy of gliomas: effective induction of therapeutic immunity to intracranial tumors by peripheral immunization with interleukin-4 transduced glioma cells

Okada, Hideho; Villa, Lorissa; Attanucci, Jason; Erff, Melanie; Fellows, WK; Mt, Lotze; If, Pollack; Chambers, WH

doi:10.1038/sj.gt.3301496

Cited by 63 publications

(45 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the following years, IL-4, as a potent anti-tumor agent, was demonstrated in different tumor models, including renal cancer (4), colorectal cancer (4,5), spontaneous adenocarcinoma (6), colon carcinoma (7,8), fibrosarcoma (9,10) and melanoma (9). Okada et al compared the anti-tumor abilities of several cytokines using rat glioma (11). They transferred the cDNA of granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon alpha (IFN), IL-12 and IL-4 into rat 9 L tumor cells.…”

Section: The Paradox Of Il-4 In Tumor Immunitymentioning

confidence: 99%

Paradoxical Roles of IL-4 in Tumor Immunity

2009

View full text Add to dashboard Cite

show abstract

Section: The Paradox Of Il-4 In Tumor Immunitymentioning

confidence: 99%

Paradoxical Roles of IL-4 in Tumor Immunity

2009

View full text Add to dashboard Cite

show abstract

“…On day 5 after inoculation of 1 Â 10 5 GL261 cells in the right hemisphere, the animals received an intratumoral injection of 1 Â 10 5 EGFR-MSC that had been transfected ex vivo with adenoviral vector (Ad) encoding interferon (IFN)-a cDNA. IFN-a was chosen as a therapeutic agent because we have been shown IFN-a gene transfer to be effective in controlling preclinical brain tumors 36 and inducing effective antiglioma immune responses (manuscripts submitted). These mIFN-a transfected EGFR-MSC expressed approximately 300 ng/10 6 cells/48 hours IFN-a based on a specific ELISA, while EGFR-MSC transfected with a backbone-control Ad-c5 did not express detectable amount of IFN-a.…”

Section: Treatment Of Established Gl261 Glioma With Ifn-a-transfectedmentioning

confidence: 99%

Epidermal growth factor receptor-transfected bone marrow stromal cells exhibit enhanced migratory response and therapeutic potential against murine brain tumors

et al. 2005

View full text Add to dashboard Cite

We have created a novel cellular vehicle for gene therapy of malignant gliomas by transfection of murine bone marrow stroma cells (MSCs) with a cDNA encoding epidermal growth factor receptor (EGFR). These cells (EGFR-MSCs) demonstrate enhanced migratory responses toward glioma-conditioned media in comparison to primary MSCs in vitro. Enhanced migration of EGFR-MSC was at least partially dependent on EGF-EGFR, PI3-, MAP kinase kinase, and MAP kinases, protein kinase C, and actin polymerization. Unlike primary MSCs, EGFR-MSCs were resistant to FasL-mediated cytotoxicity and were capable of stimulating allogeneic mixed lymphocyte reaction, suggesting EGFR-MSCs possess suitable characteristics as vehicles for brain tumor immuno-gene therapy. Following injection at various sites, including the contralateral hemisphere in the brain of syngeneic mice, EGFR-MSCs were able to migrate toward GL261 gliomas or B16 melanoma in vivo. Finally, intratumoral injection with EGFR-MSC adenovirally engineered to secrete interferon-a to intracranial GL261 resulted in significantly prolonged survival in comparison to controls. These data indicate that EGFR-MSCs may serve as attractive vehicles for infiltrating brain malignancies such as malignant gliomas.

show abstract

“…models remains inferior to that observed in systemic tumor models. 28 This may reflect the fact that the central nervous system represents an immunologically challenging environment, 29,30 at least partially due to a paucity of professional APCs under normal circumstances. 31 With regard to antigen presentation in the CNS and CNS tumors, although microglia are proposed to be resident APCs in the CNS, their capability for stimulating cellular immune responses is controversial (reviewed by Carson 32 and Graeber et al 33 ).…”

Section: Glioma Gene Therapy With Ifn-a and Dcsmentioning

confidence: 99%

Sequential delivery of interferon-α gene and DCs to intracranial gliomas promotes an effective antitumor response

et al. 2004

Self Cite

View full text Add to dashboard Cite

Effective presentation of tumor antigens by dendritic cells (DCs) is considered to be essential for the induction of antitumor T-cell responses. Apoptotic and necrotic tumors have been noted to be a robust antigen source for DCs. Because glioma cells undergo apoptosis after transfection with the type I interferon (IFN) gene and type I IFNs promote the stimulatory activity of DCs, we hypothesized that transfection of glioma cells with type I IFN genes and provision of DCs would promote particularly effective antitumor activity by both facilitating apoptosis of glioma cells and the presentation of the glioma antigens, thereby inducing specific immune responses against glioma cells. We have previously reported the proof of this hypothesis in vitro and in a subcutaneous tumor model. Here we report an extension of this approach in intracranial (i.c.) gliomas using adenoviral IFN-a (Ad-IFN-a) vector. Mice bearing day-5 i.c. GL261 glioma received sequential intratumoral (i.t.) delivery of Ad-IFN-a and bone marrow-derived syngeneic DCs. This treatment prolonged survival in that nine of 17 animals survived long term (460 days versus 0 of 10 control animals). Specific CTL activity was demonstrated following this regimen in the cervical lymph nodes, and the therapeutic efficacy was dependent upon CD8+ cells. Furthermore, these animals were protected against subsequent rechallenge with GL261 gliomas. DCs injected i.t. survived in the tumor and migrated into cervical lymph node. In vitro migration assays revealed the ability of DCs to migrate toward the tumor, suggesting that i.t. injected DCs migrate through the glioma. Taken together, this combination of gene therapy and cellular immunotherapy may be an effective future strategy for treating human gliomas.

show abstract

Cytokine gene therapy of gliomas: effective induction of therapeutic immunity to intracranial tumors by peripheral immunization with interleukin-4 transduced glioma cells

Cited by 63 publications

References 54 publications

Paradoxical Roles of IL-4 in Tumor Immunity

Paradoxical Roles of IL-4 in Tumor Immunity

Epidermal growth factor receptor-transfected bone marrow stromal cells exhibit enhanced migratory response and therapeutic potential against murine brain tumors

Sequential delivery of interferon-α gene and DCs to intracranial gliomas promotes an effective antitumor response

Contact Info

Product

Resources

About