Bone marrow-derived dendritic cells pulsed with a tumor-specific peptide elicit effective anti-tumor immunity against intracranial neoplasms

Okada, Hideho; Tahara, Hideaki; Shurin, Michael R.; Attanucci, Jason; Giezeman‐Smits, Katinka M.; Fellows, Wendy; Lotze, Michael T.; Chambers, William H.; Bozik, Michael E.

doi:10.1002/(sici)1097-0215(19981005)78:2<196::aid-ijc13>3.0.co;2-9

Cited by 98 publications

(72 citation statements)

References 29 publications

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“…Intracranial tumor inoculation was performed as described previously. 25 Briefly, using a 10 ml Hamilton syringe, 1 Â 10 5 GL261 or 1 Â 10 4 B16 cells suspended in 2 ml of PBS were stereotactically injected through an entry site at the bregma 2 mm to the right of the sagittal suture and 3 mm below the surface of the skull of anesthetized C57BL/6 mice using a Kopf stereotactic frame (Kopf Instruments, Tujunga, CA).…”

Section: Cytotoxicity Assaysmentioning

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

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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.

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Section: Cytotoxicity Assaysmentioning

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

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“…In addition, the combination of this approach with peripheral vaccine strategies may further enhance therapeutic efficacy by promoting the activity and survival of immune effector cells, which are primarily induced in the periphery. [51][52][53] Materials and methods…”

Section: Glioma Gene Therapy With Ifn-a and Dcsmentioning

confidence: 99%

“…53 Briefly, C57BL/6 or EGFP-transgenic C57BL/6 mouse-derived BM cells were cultured in CM supplemented with 1000 U/ml recombinant murine granulocyte/macrophage colony-stimulating factor and recombinant mIL-4 (Schering-Plough, Kenilworth, NJ, USA) at 371C in a humidified, 5% CO 2 incubator for 7 days. DCs were then isolated at the interface of 14.5% (w/v) metrizamide (Sigma, St Louis, MO, USA) in CM discontinuous gradients by centrifugation.…”

Section: Generation Of Dcs From Bmmentioning

confidence: 99%

“…injection of GL261 glioma cells as previously described. 53 Briefly, using a 10 ml Hamilton syringe, 1 Â 10 5 GL261 suspended in 2 ml of HBSS were stereotactically injected at the bregma 2 mm to the right of the sagittal suture and 3 mm below the surface of the skull of anesthetized C57BL/6 mice using a Kopf stereotactic frame (Kopf Instruments, Tujunga, CA, USA). The animals bearing i.c.…”

Section: Tumor Inoculation and Intratumoral Delivery Of Ad-ifn-a And Dcsmentioning

confidence: 99%

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

et al. 2004

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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.

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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.…”

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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Bone marrow-derived dendritic cells pulsed with a tumor-specific peptide elicit effective anti-tumor immunity against intracranial neoplasms

Cited by 98 publications

References 29 publications

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

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

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

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