Phase 2 trial of personal dendritic cell vaccines in newly diagnosed glioblastoma: 3-year follow-up and correlations with survival.
Publication Title
Hum Vaccin Immunother
Document Type
Article
Publication Date
12-1-2025
Keywords
california; santa monica; pacific neurosci; sjci
Abstract
Survival of glioblastoma (GBM) patients is unsatisfactory. Adding patient-specific vaccines to standard therapy may improve outcomes. Autologous dendritic cells (DC) loaded with autologous tumor antigens (ATA) from short-term cell lines established from autologous tumor are a promising therapeutic vaccine strategy. DC-ATA vaccines were tested in a single-arm phase 2 trial in newly diagnosed GBM patients. Tumor tissue was collected during surgical resection. DC were differentiated from peripheral blood monocytes. Intent-to-treat enrollment took place before standard concurrent radiation therapy and temozolomide (RT/TMZ). DC-ATA was manufactured during RT/TMZ, then injected subcutaneously over 6 months concurrently with adjuvant TMZ. DC-ATA was reliably manufactured; treatment was well tolerated. Fifty-seven patients started vaccine therapy; 69% received all eight vaccine doses. The 10.7-month median progression-free survival (PFS) is 57% greater than the average of medians from standard treatment arms in six randomized trials that also enrolled patients before RT/TMZ. Disease control and overall survival (OS) dropped precipitously once DC-ATA was completed. Survival curves stratified by prognostic variables did not separate until after DC-ATA was discontinued. Multivariate analysis identified receipt of all eight planned vaccine injections, MGMT promoter methylation, concurrent dexamethasone dose ≤2 mg, and receipt of six or more TMZ cycles as independent variables. Common features among the seven patients who were progression-free after 3 years were eight vaccine injections, ≤2 mg dexamethasone, age < 60 years, and adjuvant TMZ given without concurrent bevacizumab. PFS was encouraging, and the data suggest that OS may be increased by extending vaccine treatment.
Area of Special Interest
Cancer
Area of Special Interest
Neurosciences (Brain & Spine)
Specialty/Research Institute
Oncology
Specialty/Research Institute
Neurosciences
DOI
10.1080/21645515.2025.2556591
