Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma

Heimberger, Amy B.; Crotty, Laura E.; Archer, Gary E.; McLendon, Roger E.; Friedman, Allan H.; Dranoff, Glenn; Bigner, Darell D.; Sampson, John H.

doi:10.1016/s0165-5728(99)00172-1

Cited by 124 publications

(85 citation statements)

References 38 publications

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“…Treatment was carried out at the Department of Neurosurgery, Niigata University Hospital. Twelve patients (cases 2,4,5,7,9,11,13,14,15,17,18, and 19 in Table 1) had a maintenance dose (predonine, 30 mg/d) of glucocorticoid therapy during the immunotherapy. The median Karnofsky performance scale was 62.5, ranging from 30 to 100.…”

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confidence: 99%

Clinical Evaluation of Dendritic Cell Vaccination for Patients with Recurrent Glioma: Results of a Clinical Phase I/II Trial

Yamanaka

Homma

Yajima

et al. 2005

Clinical Cancer Research

288

218

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Purpose: To investigate the safety and the immunologic and clinical responses of dendritic cell therapy for patients with recurrent malignant glioma. Experimental Design: Twenty-four patients with recurrent malignant glioma (6 grade 3 and 18 grade 4 patients) were evaluated in a phase I/II clinical study of dendritic cell therapy. All patients were resistant to the standard maximum therapy. The patient's peripheral blood dendritic cells were generated with granulocyte macrophage colony-stimulating factor, plus interleukin 4 with or without OK-432, and pulsed with an autologous tumor lysate. Dendritic cells were injected intradermally, or both intratumorally and intradermally every 3 weeks. Results: The protocols were well tolerated with only local redness and swelling at the injection site in several cases. Clinical responses were as follows: 1patient with partial response, 3 patients with minor response, 10 patients with stable disease, and 10 patients with progressive disease. The patients whose dendritic cells were matured with OK-432 had longer survival times than the dendritic cells from patients without OK-432 maturation. The patients with both intratumoral and intradermal administrations had a longer survival time than the patients with intradermal administration only. Increased ELISPOT and delayed-type hypersensitivity responses after vaccination could provide good laboratory markers to predict the clinical outcome of patients receiving dendritic cell vaccination. The overall survival of patients with grade 4 glioma was 480 days, which was significantly better than that in the control group. Conclusions: This study showed the safety and clinical response of autologous tumor lysatepulsed dendritic cell therapy for patients with malignant glioma. Dendritic cell therapy is recommended for further clinical studies in malignant glioma patients.

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confidence: 99%

Clinical Evaluation of Dendritic Cell Vaccination for Patients with Recurrent Glioma: Results of a Clinical Phase I/II Trial

Yamanaka

Homma

Yajima

et al. 2005

Clinical Cancer Research

288

218

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“…Vaccination with syngeneic DC pulsed with acid-eluted peptides derived from autologous tumors prolonged survival for rats harboring preestablished intracranial 9L gliosarcomas through enhancing CD8 + cell infiltration into the tumors and induction of 9L-specific cytotoxic T lymphocytes (Liau et al, 1999). Vaccination with tumor homogenate also protects against syngenic intracerebral glioma (Heimberger et al, 2000). The advantages of vaccinating with total tumor-derived material such as acid-eluted peptides, tumor extracts, tumor homogenate, or RNA, are that the identity of the tumor antigen need not be known and that the presence of multiple tumor antigens reduces the risk of antigen-negative escape mutants (Vierboom et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy of intracranial G422 glioblastoma with dendritic cells pulsed with tumor extract or RNA

Zhang

Tang

Zhan

et al. 2004

J. Zheijang Univ.-Sci.

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Abstract:Objective: To investigate the anti-tumor efficacy of dendritic cell (DC)-based vaccines pulsed with tumor extracts or RNA in a mouse model of intracranial G422 glioblastoma. Methods: Bone marrow-derived DCs were pulsed ex vivo with tumor extracts or RNA. Ninety female mice harboring 4-day-old intracranial G422 glioblastomas and 126 normal mice were treated with three spaced one week apart subcutaneous injections either with PBS, unpulsed DCs, G422 tumor extracts, RNA, DCs pulsed with G422 tumor extracts (DC/extract) or with RNA (DC/RNA). Seven days after the third immunization of normal mice, the spleens of 36 of them were harvested for cytotoxic T lyphocyte (CTL) assays and the others were challenged in the brain with G422 tumor cells. All the treated mice were followed for survival. Some mice brains were removed and examined pathologically when they died. Results: Immunization using DC/extract or DC/RNA significantly induced G422-specific CTL responses compared with control groups (P<0.01). Vaccination with DC/extract or DC/RNA, either prior to G422 tumor challenge or in tumor-harboring mice, significantly prolonged survival compared with other control groups (P<0.01). Conclusion: DCs pulsed with tumor extracts or RNA derived from autologous tumors has potential antitumor effects via activation of cell-mediated immunity. Our results suggest a useful therapeutic strategy against gliomas.

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“…30,[66][67][68][69] Abbreviations IFN, interferon; DC, dendritic cell; CTL, cytotoxic T cell; IL, interleukin; TNF, tumor necrosis factor; NK, natural killer; TRAIL, tumor necrosis factor-a (TNF-a)-related apoptosis-inducing ligand; Neo-R, neomycin resistant gene; VEC-DIC, video-enhanced contrast-differential contrast; CM, complete media.…”

Section: Discussionmentioning

confidence: 99%

Effective induction of antiglioma cytotoxic T cells by coadministration of interferon-β gene vector and dendritic cells

et al. 2003

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As type I interferons (IFNs) enhance the stimulatory activity of dendritic cells (DCs), we hypothesized that transfection of glioma cells with the IFN-b gene in the presence of DCs would provide particularly effective antitumor activity by both facilitating apoptosis of glioma cells and presenting the resulting glioma antigens to T cell by DCs, thereby inducing specific T-cell responses against glioma cells. A mouse glioma cell line 203G was first transfected with cDNA encoding IFN-b using cationic liposomes, then cocultured with syngeneic bone marrow-derived DCs and naïve splenic T cells. The 203G cells were almost completely killed following 96-hour coculture with DCs and T cells, and strong tumor-specific cytotoxic T-lymphocyte (CTL) activity accompanied by high level interleukin (IL)-12 and IFN-g production was observed in culture. In addition, omission of either IFN-b gene delivery, DCs or T cells from the coculture completely abrogated the induction of the CTL activity, suggesting that the combination of these components was required to elicit an optimal effect. On the basis of these in vitro data, syngeneic animals bearing subcutaneous 203G tumors received intratumoral injections of IFN-b gene and DCs. Suppression of the tumor growth by this combinational therapy was superior to treatment with DC or IFN-b gene solely. This combination may constitute a new therapeutic strategy to induce potent antiglioma immune responses.

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Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma

Cited by 124 publications

References 38 publications

Clinical Evaluation of Dendritic Cell Vaccination for Patients with Recurrent Glioma: Results of a Clinical Phase I/II Trial

Clinical Evaluation of Dendritic Cell Vaccination for Patients with Recurrent Glioma: Results of a Clinical Phase I/II Trial

Immunotherapy of intracranial G422 glioblastoma with dendritic cells pulsed with tumor extract or RNA

Effective induction of antiglioma cytotoxic T cells by coadministration of interferon-β gene vector and dendritic cells

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