Table 1: Synopsis of DC-based immunotherapy trials for GBM patients.

PatientsPhaseRouteAntigen formatImmune responseClinical responseReferences

22 patients (13 recurrent GBM, 5 AA, 3 AO, 1 AOA)Phase I/IIIntranodal + intramuscular injections of poly-ICLCSynthetic peptides for GAAsInduced positive immune responses against at least one of the GAAs in PBMCs in 58% of patients (after 4 vaccinations). Significant upregulation: interferon-alpha and CXCL10.4 recurrent GBM are progression free for at least 12 months; 1 CR (recurrent GBM). Median TTP: 4 months.[61]
23 patients (15 newly diagnosed GBM, 8 recurrent GBM)Phase IIntradermal + intramuscular injections of poly-ICLCAutologous tumor lysate + imiquimod or poly-ICLCNo dose-limiting toxicity. Tumor samples with a mesenchymal gene expression signature had a higher number of CD3+ and CD8+ tumor-infiltrating lymphocytesNewly diagnosed: median OS: 35.9 months, with a mean follow-up time of more than 4 years, and 1-, 2-, and 3-year survival rates of 93%, 77%, and 58%, respectively. Recurrent: median OS was 17.9 months from the time of initial glioblastoma diagnosis. OS was significantly longer for those who received DC vaccination at initial diagnosis compared with those who enrolled in this trial at the time of recurrence.[62]
8 patients (newly diagnosed GBM)Phase I/IIIntradermalAutologous tumor lysateDTH (2/5) increased CD8+/CD25+ in PBL (6/7) ATR PBMC (5/8) IFN-gamma ELISPOT)Median OS: 24 months[63]
45 children (23 recurrent GBM, 5 AA, 1 AOA, 16 other HGG)Phase IIntradermalAutologous tumor lysate + imiquimodNo data availableMedian PFS for relapsed GBM: 4.3 months; median OS for relapsed GBM: 12.2 months[64]
12 patients (newly diagnosed GBM)Phase IIntradermalEGFRvIII antigen + KLHDTH EGFRvIII (5/9); DTH KLH (9/9); ATR PBMC (10/12) (EGFRvIII-induced proliferation)Median OS: 22.8 months[65]
56 patients (recurrent GBM)Phase I/IIIntradermalAutologous tumor lysateDTH (9/21 at time of diagnosis, 9/17 after 2 vaccinations)3-month PFS; OS: 9.6 months; 24-month OS: 14.8%; total resection is a predictor for better PFS; younger age and total resection are predictors for better OS.[66]
34 patients (23 recurrent GBM, 11 newly diagnosed GBM)Phase IISubcutaneousAutologous tumor lysatePostvaccine antigen-directed IFNg response in PBMCs (17/34); DTH-test resulted in cutaneous GBM in 1 patient (DTH was subsequently discontinued)Newly diagnosed: 8/17 (47%) vaccine responders versus. 3/15 (20%) nonresponders; Recurrent: TTS, and d; TTP, and d (8 responders and 13 nonresponders); TTP, and d (8 responders and 15 nonresponders)[67]
24 patients (18 recurrent GBM, 6 grade III glioma)Phase I/IIIntradermal or intradermal + intratumoral (Ommaya reservoir)Autologous tumor-lysateDTH to tumor lysate (8/24); ATR PBMC (7/24) (IFN-gamma ELISPOT)1 PR, 3 MR, 6 SD (GBM); 4 SD (Grade III glioma); median OS: 16 months versus 13.3 months; longer survival if DC maturation or IC injection. One grade IV neurotoxicity event (stupor) observed.[68]
12 patients (7 newly diagnosed GBM, 5 recurrent GBM)Phase IIntradermalAcid-eluted tumor associated peptidesCTL response (6/12); tumor infiltration CD8+ CD45RO+ cells (4/8)Median TTP: 19.9 months—OS 18 to >58 months—median OS: 35.8 months. 1PR; Median OS: 23.4 versus 18.3 months. No dose-limiting toxicity observed[69]
14 patients (1 newly diagnosed GBM, 9 recurrent GBM, 4 AA)Phase ISubcutaneousAutologous tumor lysateIncreased IFNγ RNA in PBMC (6/10) ATR T cells (4/9) (HER-2, gp100, MAGE-1 tetramers); CD8+, CD45RO+ cells infiltration (3/6)Median survival: 33.3 versus 7.5 months (8/9 recurrent GBM).[70]
15 patients (6 recurrent GBM, 7 AA, 2 OAA)Phase IIntradermalDC fusion with autologous glioma cellsDTH to tumor lysate (15/15); increased cytotoxic activity (2/15); increased intracellular IFN-gamma in CD8+ T cells (1/15)1 SD (GBM); 3 PR, 1 MR (AA); 1 PR, 1 SD (AOA)[71]
7 patients (2 recurrent GBM, 1 AA, 4 other HGG)Phase IIntradermalAutologous tumor RNANo anti-tumor responses (0/3) (IFN-gamma ELISA)1 PR (1XA); 4 SD (1AA, 3 other HGG)[72]
25 patients (newly diagnosed GBM: 13 plus chemotherapy, 12 without chemotherapy)Phase I/IIIntradermalAutologous tumor lysates or peptide elutionsVaccine alone: ATR PBMC (4/11) Vaccine + chemotherapy: ATR PBMC (4/13) (lytic activity and IFN-gamma PCR)Vaccine or chemotherapy alone: 24-month survival: 8% Vaccine + chemotherapy: 3 PR; 24-month survival: 42%[73]
10 patients (7 recurrent GBM after radiotherapy, 3 recurrent grade III glioma)Phase I/IIIntradermal and/or intratumor (Ommaya)Autologous tumor lysateIncrease in NK cells in PBMCs (5/10); DTH to tumor lysate (3/10); increased T-cell mediated antitumor activity (2/10)2 MR, 2SD (GBM), 2SD (Grade III glioma); OS > 50 months.[74]
9 patients (7 newly diagnosed GBM, 2 AA after radiotherapy)Phase ISubcutaneousTumor-specific MHC-I-associated peptidesSystemic CTL cytotoxicity against tumor (4/9) (lytic activity); tumor infiltration: CD4+, CD8+, CD45RO+ cells (2/4)Prolonged median survival compared to control group: 15.2 versus 8.6 months (GBM)[75]

Abbreviations: AA: anaplastic astrocytoma; AO: anaplastic oligodendroglioma; AOA: anaplastic oligoastrocytoma; ATR: anti-tumor responses; CR: complete response; DTH: delayed-type hypersensitivity; GAA: glioblastoma associated antigen; GBM: glioblastoma multiform; HGG: high-grade glioma; KLH: keyhole limpet haemocyanin; MR: Minor response; OS: overall survival; PBMC: peripheral blood mononuclear cells; PFS: progression-free status; PR: partial response; PXA: pleomorphic xanthoastrocytoma; SD: stable disease; TMZ: Temozolomide; TTP: Time to tumor progression; TTS: Time to tumor survival; XA: xanthoastrocytoma.