Sponsored by
J Immunother. 2011 Apr 14. [Epub ahead of print]
Fadul CE, Fisher JL, Hampton TH, Lallana EC, Li Z, Gui J, Szczepiorkowski ZM, Tosteson TD, Rhodes CH, Wishart HA, Lewis LD, Ernstoff MS.
*Department of Medicine, Section of Hematology/Oncology ??Section of Clinical Pharharmacology ?Department of Community and Family Medicine, Section of Biostatistics and Epidemiology ¶Department of Pathology Departments of ?Radiology **Psychiatry, Brain Imaging Laboratory ?Medical Oncology Immunotherapy Program ?Neuro-oncology Program, Norris Cotton Cancer Center §Department of Pharmacology and Toxicology, Dartmouth Medical School and Dartmouth-Hitchcock Medical Center, Lebanon, NH.
Abstract
Patients with glioblastoma multiforme (GBM) are profoundly immunosuppressed and may benefit from restoration of an antitumor immune response in combination with conventional radiation therapy and temozolomide (TMZ). The optimal strategies to evaluate clinically relevant immune responses to treatment have yet to be determined. The primary objective of our study was to determine immunologic response to cervical intranodal vaccination with autologous tumor lysate-loaded dendritic cells (DCs) in patients with GBM after radiation therapy and TMZ. We used a novel hierarchical clustering analysis of immune parameters measured before and after vaccination. Secondary objectives were to assess treatment feasibility and to correlate immune response with progression-free survival (PFS) and overall survival. Ten eligible patients received vaccination. Tumor-specific cytotoxic T-cell response measured after vaccination was enhanced for the precursor frequency of CD4 T and CD4 interferon γ-producing cells. Hierarchical clustering analysis of multiple functional outcomes discerned 2 groups of patients according to their immune response, and additionally showed that patients in the top quintile for at least one immune function parameter had improved survival. There were no serious adverse events related to DC vaccination. All patients were alive at 6 months after diagnosis and the 6-month PFS was 90%. The median PFS was 9.5 months and overall survival was 28 months. In patients with GBM, immune therapy with DC vaccination after radiation and TMZ resulted in tumor-specific immune responses that were associated with prolonged survival. Our data suggest that DC vaccination in combination with radiation and chemotherapy in patients with GBM is feasible, safe, and may induce tumor-specific immune responses.
PMID: 21499132 [PubMed - as supplied by publisher]
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