Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical phase I/II trial

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 þ and CD8 þ 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.

Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study

“…Also for malignant brain tumour, MHC class I-associated peptides have been eluted from cultured autologous glioma cells, and a mixture of peptides was used to load DC since no specific tumour antigenic targets are known (Yu et al, 2001). In other trials, tumour proteins instead of peptides have been used to load DC (Hsu et al, 1996;Schott et al, 2000;Geiger et al, 2001;Chang et al, 2002;Höltl et al, 2002;Wheeler et al, 2003;Yamanaka et al, 2003;De Vleeschouwer et al, 2004). The use of proteins from autologous tumours instead of peptides is now generally considered a valuable approach, certainly when tumour-specific epitopes are not known (Curiel and Curiel, 2002).…”

“…The DTH testing to antigen is one clinical monitoring tool to indicate cellular immunity, although it remains controversial whether or not DTH to autologous tumour can be a reliable correlate of clinical responses ( Clay et al, 2001). DTH tests are commonly used if a mixture of undefined tumour proteins is used as a source of antigen for the DC (Geiger et al, 2001;Yamanaka et al, 2003). Additional immune monitoring with Elispot should be implemented when future patients are treated (Geiger et al, 2001;Chang et al, 2002;Yamanaka et al, 2003).…”

“…DTH tests are commonly used if a mixture of undefined tumour proteins is used as a source of antigen for the DC (Geiger et al, 2001;Yamanaka et al, 2003). Additional immune monitoring with Elispot should be implemented when future patients are treated (Geiger et al, 2001;Chang et al, 2002;Yamanaka et al, 2003). The group of patients was heterogeneous, because we wanted to assess general feasibility of tumour vaccination.…”

“…Phase I studies have demonstrated feasibility, safety and bioactivity of autologous peptide-pulsed DC vaccine for patients with malignant glioma (Yu et al, 2001). Early clinical experiences with immunotherapy using protein-pulsed DC suggest this to be a promising strategy for patients with recurrent malignant glioma (Wheeler et al, 2003;Yamanaka et al, 2003;De Vleeschouwer et al, 2004).…”

Current Immunotherapeutic Strategies for Central Nervous System Tumors

“…The rational for this strategy was to promote tumoral antigenic presentation in order to trigger cellular immune response. DCs pulsed with peptides from patient's tumors have been tested in trials for malignant gliomas [67,68]. One of these trials evaluated 5 patients with GBM and AA [67].…”