A phase I trial of tumor-associated antigen-pulsed dendritic cell immunotherapy for patients with brain stem glioma and glio....

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Background: Previous immunotherapy trials for malignant glioma
(Yu, J.,et al, Cancer Res. 2001;61:842-7 and 2004;64;4973-9) have
demonstrated efficacy in generating a tumor specific immune response.
Here we set out to determine feasibility and immunogenecity of
dendritic vaccination with specific glioma-associated antigens.
Methods: The
goal of this study is to use tumor associated antigens (TAA) known to
be expressed on gliomas and pulse dendritic cells with these antigens
in an MHC compatible fashion using epitopes of HER-2, TRP-2, gp100,
MAGE-1, IL13R alpha, and AIM-3. In this phase I trial, HLA-A1 and/or
HLA-A2-positive patients with newly diagnosed or recurrent glioblastoma
were eligible. Leukapheresis was used to isolate mononuclear cells
which were differentiated into dendritic cells in culture, pulsed with
tumor peptide, and then administered intradermally three times at
2-week intervals.
Results: Twenty patients, 15 males and five
females, were enrolled between November 2006 and December 2008 with one
screen failure. The median patient age was 47 years (range: 26-65) and
patients had a median Karnofsky performance status of 90% (range:
90-100). There were 16 newly diagnosed and three recurrent glioblastoma
multiforme (GBM) patients, who underwent surgery prior to vaccination.
Our data on 19 patients and 54 courses of dendritic cell vaccines
demonstrate zero grade 3 /4 toxicities that were attributable to the
vaccination. Thirteen patients continue to have stable disease (ranging
from 15 to 115 weeks), six patients have demonstrated tumor
progression. Median survival from surgery was 60 weeks (ranging from 26
to 115 weeks). Of 15 patients tested to date, six patients demonstrated
an antigen-specific cytotoxic T-cell response to at least one antigen
after vaccination. Only 17% of CTL responders (1/6) demonstrated tumor
progression compared to 56% (5/9) of nonresponders to date.
This phase I study demonstrated the feasibility, safety, and
bioactivity of a TAA-pulsed dendritic cell vaccine for patients with
glioblastoma progression free survival correlated with CTL response.