Abstract
<div>Abstract<p><b>Purpose:</b> To assess the feasibility, safety, and toxicity of autologous tumor lysate–pulsed dendritic cell (DC) vaccination and toll-like receptor (TLR) agonists in patients with newly diagnosed and recurrent glioblastoma. Clinical and immune responses were monitored and correlated with tumor gene expression profiles.</p><p><b>Experimental Design:</b> Twenty-three patients with glioblastoma (WHO grade IV) were enrolled in this dose-escalation study and received three biweekly injections of glioma lysate-pulsed DCs followed by booster vaccinations with either imiquimod or poly-ICLC adjuvant every 3 months until tumor progression. Gene expression profiling, immunohistochemistry, FACS, and cytokine bead arrays were performed on patient tumors and peripheral blood mononuclear cells.</p><p><b>Results:</b> DC vaccinations are safe and not associated with any dose-limiting toxicity. The median overall survival from the time of initial surgical diagnosis of glioblastoma was 31.4 months, with a 1-, 2-, and 3-year survival rate of 91%, 55%, and 47%, respectively. Patients whose tumors had <i>mesenchymal</i> gene expression signatures exhibited increased survival following DC vaccination compared with historic controls of the same genetic subtype. Tumor samples with a <i>mesenchymal</i> gene expression signature had a higher number of CD3<sup>+</sup> and CD8<sup>+</sup> tumor-infiltrating lymphocytes compared with glioblastomas of other gene expression signatures (<i>P</i> = 0.006).</p><p><b>Conclusion:</b> Autologous tumor lysate–pulsed DC vaccination in conjunction with TLR agonists is safe as adjuvant therapy in newly diagnosed and recurrent glioblastoma patients. Our results suggest that the <i>mesenchymal</i> gene expression profile may identify an immunogenic subgroup of glioblastoma that may be more responsive to immune-based therapies. <i>Clin Cancer Res; 17(6); 1603–15. ©2010 AACR</i>.</p></div>
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
