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Clinical Trial
. 2003 Oct 6;89(7):1172-9.
doi: 10.1038/sj.bjc.6601268.

Vaccination of Recurrent Glioma Patients With Tumour Lysate-Pulsed Dendritic Cells Elicits Immune Responses: Results of a Clinical Phase I/II Trial

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Free PMC article
Clinical Trial

Vaccination of Recurrent Glioma Patients With Tumour Lysate-Pulsed Dendritic Cells Elicits Immune Responses: Results of a Clinical Phase I/II Trial

R Yamanaka et al. Br J Cancer. .
Free PMC article

Abstract

In this Phase I/II trial, the patient's peripheral blood dendritic cells were pulsed with an autologous tumour lysate of the glioma. Seven patients with glioblastoma and three patients with anaplastic glioma, ranging in age from 20 to 69 years, participated in this study. The mean numbers of vaccinations of tumour lysate-pulsed dendritic cells were 3.7 times intradermally close to a cervical lymph node, and 3.2 times intratumorally via an Ommaya reservoir. The percentage of CD56-positive cells in the peripheral blood lymphocytes increased after immunisation. There were two minor responses and four no-change cases evaluated by radiological findings. Dendritic cell vaccination elicited T-cell-mediated antitumour activity, as evaluated by the ELISPOT assay after vaccination in two of five tested patients. Three patients showed delayed-type hypersensitivity reactivity to the autologous tumour lysate, two of these had a minor clinical response, and two had an increased ELISPOT result. Intratumoral CD4+ and CD8+ T-cell infiltration was detected in two patients who underwent reoperation after vaccination. This study demonstrated the safety and antitumour effects of autologous tumour lysate-pulsed dendritic cell therapy for patients with malignant glioma.

Figures

Figure 1
Figure 1
Flow chart of the phase I/II trial of DC therapy.
Figure 2
Figure 2
Computed tomography of Case 3 shows that, although the size of the low density area did not change, the contrast enhanced lesion was decreased. Computed tomography contrast enhanced images before (A) and after (B) vaccination. Magnetic resonance imaging of Case 6 shows that the contrast enhanced lesion was decreased after vaccination. Contrast enhanced MRI before (C) and after (D) vaccination.
Figure 3
Figure 3
T-cell-mediated antitumour activity of PBMCs of glioma patients, as evaluated by the ELISPOT assay before and after vaccination. Data are shown as the median values±standard deviation (n=3). Statistical significance was assessed by Student's t-test. *P<0.05.
Figure 4
Figure 4
Immunohistochemical characterisation of infiltrating cells in an intracranial tumour at first surgery, before vaccination and at reoperation after vaccination. (A) CD4+ T cell before vaccination; (B) CD4+ T cell after vaccination; (C) CD8+ T cell before vaccination; (D) CD8+ T-cell after vaccination (magnification × 400).

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