Clinical Responsiveness of Glioblastoma Multiforme to Chemotherapy after
Vaccination
Christopher J. Wheeler, Asha Das, Gentao
Liu, John S. Yu and Keith L. Black
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical
Center, Los Angeles, California
Purpose. Although the development of immune-based therapies for
various cancers including malignant glioma has been heralded with
much hope and optimism, objective clinical improvements in most
vaccinated cancer patients have not been realized.
To broaden the
search for vaccine-induced benefits, we examined synergy of vaccines
with conventional chemotherapy. Experimental
Design. Survival and progression times were analyzed
retrospectively in 25 vaccinated (13 with and 12 without subsequent chemotherapy)
and 13 nonvaccinated de novo glioblastoma (GBM) patients
receiving chemotherapy.
Immune responsiveness and T-cell receptor
excision circle (TREC) content within CD8+ T cells (CD8+
TRECs) was determined in vaccinated patients. Results. Vaccinated patients receiving subsequent chemotherapy exhibited
significantly longer times to tumor recurrence after chemotherapy
relative to their own previous recurrence times, as well as
significantly longer postchemotherapy recurrence times and survival
relative to patients receiving isolated vaccination or chemotherapy.
Patients exhibiting objective (>50%) tumor regression, extremely
rare in de novo GBM, were also confined to the vaccine +
chemotherapy group.
Prior tumor behavior, demographic factors, other
treatment variables, distribution of vaccine responders, and patients
with high CD8+ TRECs all failed to account for these
differences in clinical outcome.
Within all GBM patients receiving
post-vaccine chemotherapy, however, CD8+ TRECs predicted
significantly longer chemotherapeutic responses, revealing a strong
link between the predominant T-cell effectors in GBM and tumor
chemosensitivity. Conclusions. We propose that therapeutic vaccination synergizes with
subsequent chemotherapy to elicit tangible clinical benefits for GBM
patients.
© 2004 American
Association for Cancer Research
Source: http://clincancerres.aacrjournals.org/cgi/content/abstract/10/16/5316?etoc
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