Findings from a new study provide the first evidence that the T-cell response seen after therapeutic vaccination for glioblastoma multiforme is directly related to the clinical outcome. However, the correlation was only apparent after both vaccination and chemotherapy.
In prior human studies, the immune response seen after therapeutic vaccination for various cancers has not correlated with clinical improvements, calling into question the value of these vaccines, lead author Dr. Christopher J. Wheeler, from Cedars-Sinai Medical Center in Los Angeles, and colleagues note in the July 15th issue of Cancer Research.
In the current phase II investigation, Dr. Wheeler's team assessed the immune responses and clinical outcomes of 32 patients with glioblastoma multiforme who were given dendritic cell vaccines.
Overall, 17 of the patients (53 per cent) had a vaccine response, defined as a 1.5-fold or greater increase in cytokine responses.
Compared with nonresponders, those with a response had significantly longer times to tumor progression and longer survival. Moreover, adding chemotherapy after vaccination significantly increased the time to tumor progression.
The T-cell response seen after treatment also correlated with the clinical outcome, but only after both vaccination and chemotherapy, not vaccination alone.
"This leads us to believe that while T-cell activity may not result in net destruction of the tumor, it is fundamentally changing the tumor into one that is predominantly comprised of chemosensitive cells rather than chemoresistant cells," Dr. Wheeler said in a statement.
"Our findings offer unique opportunities to identify cellular and molecular components of clinically meaningful antitumor immunity in humans," the researchers conclude.
Cancer Res 2008;68:5955-5964
