A phase I trial of tumor-associated antigen-pulsed dendritic cell immunotherapy for patients with brain stem glioma and glioblastoma

Abstract

2032 Background: Previous immunotherapy trials for malignant glioma (Yu, J.,et al, Cancer Res. 2001;61:842–7 and 2004;64;4973–9) have demonstrated efficacy in generating a tumor specific immune response. Here we set out to determine feasibility and immunogenecity of dendritic vaccination with specific glioma-associated antigens. Methods: The goal of this study is to use tumor associated antigens (TAA) known to be expressed on gliomas and pulse dendritic cells with these antigens in an MHC compatible fashion using epitopes of HER-2, TRP-2, gp100, MAGE-1, IL13R alpha, and AIM-3. In this phase I trial, HLA-A1 and/or HLA-A2-positive patients with newly diagnosed or recurrent glioblastoma were eligible. Leukapheresis was used to isolate mononuclear cells which were differentiated into dendritic cells in culture, pulsed with tumor peptide, and then administered intradermally three times at 2-week intervals. Results: Twenty patients, 15 males and five females, were enrolled between November 2006 and December 2008 with one screen failure. The median patient age was 47 years (range: 26–65) and patients had a median Karnofsky performance status of 90% (range: 90–100). There were 16 newly diagnosed and three recurrent glioblastoma multiforme (GBM) patients, who underwent surgery prior to vaccination. Our data on 19 patients and 54 courses of dendritic cell vaccines demonstrate zero grade 3 /4 toxicities that were attributable to the vaccination. Thirteen patients continue to have stable disease (ranging from 15 to 115 weeks), six patients have demonstrated tumor progression. Median survival from surgery was 60 weeks (ranging from 26 to 115 weeks). Of 15 patients tested to date, six patients demonstrated an antigen-specific cytotoxic T-cell response to at least one antigen after vaccination. Only 17% of CTL responders (1/6) demonstrated tumor progression compared to 56% (5/9) of nonresponders to date. Conclusions: This phase I study demonstrated the feasibility, safety, and bioactivity of a TAA-pulsed dendritic cell vaccine for patients with glioblastoma progression free survival correlated with CTL response. [Table: see text]

Blood Biomarkers of Glioma in Response Assessment Including Pseudoprogression and Other Treatment Effects: A Systematic Review

“…In a study of a WT1 epitope-loaded DC vaccine, tetramer assay-verified WT1-specific CD8 + T-cell responses were seen in 2 SD patients (75). During DC vaccine for recurrent GBM, TP was more common in those without epitope-specific cytotoxic CD8 + T-cell responses, with diagnostic performance for lack of response as a tool to diagnose TP calculated as Sn = 83%, Sp = 55%, +LR = 1.88, -LR = 0.30, DOR = 6.27 (71).…”

“…Thirty-seven biomarkers related to change in circulating immune cell and other hematopoietic lineage cells were reported in 14 studies (Table A9) (51,55,(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77). Six of these studies included treatment with dendritic cell (DC) vaccine immunotherapy with or without additional modalities (51, 71-73, 75, 77).…”