Journal
JOURNAL OF IMMUNOTHERAPY
Volume 36, Issue 2, Pages 152-157Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0b013e3182811ae4
Keywords
clinical trial; dendritic cells; glioma-associated antigen; tumor lysate; immunotherapy; glioblastoma; brain tumor vaccine; survival
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Funding
- NIH/NCI [K01-CA111402, RO1-CA123396, R01 CA 112358]
- Brad Kaminsky Foundation
- Cranium Crusaders
- Miles for Hope Foundation
- Northwest Biotherapeutics Inc.
- Eli & Edyth Broad Center of Regenerative Medicine and Stem Cell Research at UCLA
- STOP Cancer Foundation
- Ben & Catherine Ivy Foundation
- American Brain Tumor Association
- NIH [CA16042]
- UCLA Brain Tumor Translational Resource
- National Center for Advancing Translational Science through UCLA CTSI [UL1TR000124]
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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.
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