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Neurosurgery:
doi: 10.1227/01.neu.0000358747.32411.f4
Departments: CNS Top Abstracts

A Phase I Trial of Tumor Associated Antigen‐Pulsed Dendritic Cell Immunotherapy for Patients with Glioblastoma: 976

Yu, John S. M.D.; Rudnick, Jeremy M.D.; Chu, Ray M. M.D.; Mazer, Mia B.S.; Wang, Hongqiang; Serrano, Natalia; Francisco, Maritess; Wheeler, Christopher J. Ph.D.; Singh, Manish M.D.; Black, Keith L. M.D.; Phuphanich, Surasak M.D.

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INTRODUCTION

Previous immunotherapy trials for malignant glioma have demonstrated efficacy in generating a tumor-specific immune response. In this study, we set out to determine feasibility and immunogenecity of dendritic vaccination with specific glioma-associated antigens. The goal of this study is to use tumor associated antigens (TAAs) known to be expressed on gliomas and pulse dendritic cells with these antigens in an MHC compatible fashion using epitopes of HER2, TRP-2, gp100, MAGE-1, IL13R alpha, and AIM-3.

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METHODS

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 3 times at 2-week intervals.

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RESULTS

Twenty patients, 15 men and 5 women, were enrolled between November 2006 and December 2008 with 1 screen failure. The median patient age was 47 years (range, 26–65 years) and patients had a median Karnofsky Performance Status of 90% (range, 90%–100%). There were 16 newly diagnosed and 3 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 25 to 128 weeks), and 6 patients have demonstrated tumor progression. Median survival from surgery was 72 weeks (range, 25–128 weeks). Of the 17 patients tested to date, 11 demonstrated an antigen-specific cytotoxic T cell response to at least one antigen after vaccination. Only 17% of cytotoxic T lymphocyte (CTL) responders (1 of 6) demonstrated tumor progression compared with 56% (5 of 9) of nonresponders to date.

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CONCLUSION

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.

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