PMID- 19825799 OWN - NLM STAT- MEDLINE DCOM- 20100112 LR - 20220317 IS - 1538-8514 (Electronic) IS - 1535-7163 (Print) IS - 1535-7163 (Linking) VI - 8 IP - 10 DP - 2009 Oct TI - An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. PG - 2773-9 LID - 10.1158/1535-7163.MCT-09-0124 [doi] AB - Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by nonspecific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a consistent and tumor-specific mutation widely expressed in GBMs and other neoplasms. The safety and immunogenicity of a dendritic cell (DC)-based vaccine targeting the EGFRvIII antigen was evaluated in this study. Adults with newly diagnosed GBM, who had undergone gross-total resection and standard conformal external beam radiotherapy, received three consecutive intradermal vaccinations with autologous mature DCs pulsed with an EGFRvIII-specific peptide conjugated to keyhole limpet hemocyanin. The dose of DCs was escalated in cohorts of three patients. Patients were monitored for toxicity, immune response, radiographic and clinical progression, and death. No allergic reactions or serious adverse events were seen. Adverse events were limited to grade 2 toxicities. The maximum feasible dose of antigen-pulsed mature DCs was reached at 5.7 x 10(7) +/- 2.9 x 10(7) SD without dose-limiting toxicity. EGFRvIII-specific immune responses were evident in most patients. The mean time from histologic diagnosis to vaccination was 3.6 +/- 0.6 SD months. Median time to progression from vaccination was 6.8 months [95% confidence interval (C.I.(95)), 2.5-8.8], and median survival time from vaccination was 18.7 months (C.I.(95), 14.5-25.6). Overall median survival from time of histologic diagnosis was 22.8 months (C.I.(95), 17.5-29). This study establishes the EGFRvIII mutation as a safe and immunogenic tumor-specific target for immunotherapy. FAU - Sampson, John H AU - Sampson JH AD - Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. FAU - Archer, Gary E AU - Archer GE FAU - Mitchell, Duane A AU - Mitchell DA FAU - Heimberger, Amy B AU - Heimberger AB FAU - Herndon, James E 2nd AU - Herndon JE 2nd FAU - Lally-Goss, Denise AU - Lally-Goss D FAU - McGehee-Norman, Sharon AU - McGehee-Norman S FAU - Paolino, Alison AU - Paolino A FAU - Reardon, David A AU - Reardon DA FAU - Friedman, Allan H AU - Friedman AH FAU - Friedman, Henry S AU - Friedman HS FAU - Bigner, Darell D AU - Bigner DD LA - eng GR - P50 NS020023-268625/NS/NINDS NIH HHS/United States GR - P50 CA108786/CA/NCI NIH HHS/United States GR - P50 NS020023/NS/NINDS NIH HHS/United States GR - 5P50 NS20023-25/NS/NINDS NIH HHS/United States GR - R01 CA097222-01/CA/NCI NIH HHS/United States GR - R37 CA011898-38/CA/NCI NIH HHS/United States GR - P50 CA108786-05S10003/CA/NCI NIH HHS/United States GR - R01 CA097222-02/CA/NCI NIH HHS/United States GR - CA97222-05/CA/NCI NIH HHS/United States GR - R37 CA011898/CA/NCI NIH HHS/United States GR - R01 CA097222-03/CA/NCI NIH HHS/United States GR - P50 NS20023-25/NS/NINDS NIH HHS/United States GR - R37 CA 011898-38/CA/NCI NIH HHS/United States GR - R01 CA097222/CA/NCI NIH HHS/United States GR - R01 CA235612/CA/NCI NIH HHS/United States GR - P50 CA108786-050003/CA/NCI NIH HHS/United States GR - R01 CA097222-04/CA/NCI NIH HHS/United States GR - R01 CA097222-05/CA/NCI NIH HHS/United States GR - P50-CA108786-05/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cancer Ther JT - Molecular cancer therapeutics JID - 101132535 RN - 0 (Cancer Vaccines) RN - 0 (Mutant Proteins) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Adult MH - Cancer Vaccines/*adverse effects/*immunology MH - Disease Progression MH - ErbB Receptors/*genetics/*immunology MH - Female MH - Glioblastoma/*immunology MH - Humans MH - Immunity MH - Male MH - Middle Aged MH - Mutant Proteins/*immunology MH - Survival Analysis PMC - PMC2991139 MID - NIHMS181924 EDAT- 2009/10/15 06:00 MHDA- 2010/01/13 06:00 PMCR- 2010/11/24 CRDT- 2009/10/15 06:00 PHST- 2009/10/15 06:00 [entrez] PHST- 2009/10/15 06:00 [pubmed] PHST- 2010/01/13 06:00 [medline] PHST- 2010/11/24 00:00 [pmc-release] AID - 8/10/2773 [pii] AID - 10.1158/1535-7163.MCT-09-0124 [doi] PST - ppublish SO - Mol Cancer Ther. 2009 Oct;8(10):2773-9. doi: 10.1158/1535-7163.MCT-09-0124.