Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients

Abstract

Dendritic cell (DC) vaccination is emerging as a promising therapeutic option for malignant glioma patients. However, the optimal antigen formulation for loading these cells has yet to be established. The objective of this study was to compare the safety, feasibility, and immune responses of malignant glioma patients on 2 different DC vaccination protocols. Twenty-eight patients were treated with autologous tumor lysate (ATL)-pulsed DC vaccination, whereas 6 patients were treated with glioma-associated antigen (GAA) peptide-pulsed DCs. Safety, toxicity, feasibility, and correlative immune monitoring assay results were compared between patients on each trial. Because of HLA subtype restrictions on the GAA-DC trial, 6/15 screened patients were eligible for treatment, whereas 28/32 patients passed eligibility screening for the ATL-DC trial. Elevated frequencies of activated natural killer cells were observed in the peripheral blood from GAA-DC patients compared with the ATL-DC patients. In addition, a significant correlation was observed between decreased regulatory T lymphocyte (Treg) ratios (postvaccination/prevaccination) and overall survival (P = 0.004) in patients on both trials. In fact, Treg ratios were independently prognostic for overall survival in these patients, whereas tumor pathology was not in multivariate analyses. In conclusion, these results suggest that ATL-DC vaccination is associated with wider patient eligibility compared with GAA-DC vaccination. Decreased postvaccination/prevaccination Treg ratios and decreased frequencies of activated natural killer cells were associated with prolonged survival in patients from both trials, suggesting that these lymphocyte subsets may be relevant immune monitoring endpoints for immunotherapy protocols in malignant glioma patients.

Trial registration: ClinicalTrials.gov NCT00068510 NCT00612001.

Figures

Figure 1. Immunhistochemical detection of GAA in malignant glioma patient tumor tissue

Representative IHC staining of survivin, her-2/neu, and gp100 from a patient (GAA-03).

Figure 2. Increased frequencies of activated NK cells in peripheral blood from patients on the GAA peptide-pulsed DC trial

PBL from pre and post-DC vaccination timepoints were stained with an antibody cocktail that identifies activated NK cells populations (CD3-CD4+CD16+CD25+). (A) Representative FACS plots of activated NK cell populations from a representative patient on the GAA DC trial (Top) and ATL DC trial (Bottom). (B) Quantitative analysis of activated NK cell frequencies from peripheral blood. ***p<0.0001 by 2-way ANOVA testing.