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Curry, William T.; Gorrepati, Ramana; Piesche, Matthias; Sasada, Tetsuro; Agarwalla, Pankaj; Jones, Pamela S.; Gerstner, Elizabeth R.; Golby, Alexandra J.; Batchelor, Tracy T.; Wen, Patrick Y.; Mihm, Martin C.; Dranoff, Glenn

Vaccination with Irradiated Autologous Tumor Cells Mixed with Irradiated GM-K562 Cells Stimulates Antitumor Immunity and T Lymphocyte Activation in Patients with Recurrent Malignant Glioma

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  • Medientyp: E-Artikel
  • Titel: Vaccination with Irradiated Autologous Tumor Cells Mixed with Irradiated GM-K562 Cells Stimulates Antitumor Immunity and T Lymphocyte Activation in Patients with Recurrent Malignant Glioma
  • Beteiligte: Curry, William T.; Gorrepati, Ramana; Piesche, Matthias; Sasada, Tetsuro; Agarwalla, Pankaj; Jones, Pamela S.; Gerstner, Elizabeth R.; Golby, Alexandra J.; Batchelor, Tracy T.; Wen, Patrick Y.; Mihm, Martin C.; Dranoff, Glenn
  • Erschienen: American Association for Cancer Research (AACR), 2016
  • Erschienen in: Clinical Cancer Research
  • Sprache: Englisch
  • DOI: 10.1158/1078-0432.ccr-15-2163
  • ISSN: 1078-0432; 1557-3265
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:p>Purpose: Recurrent malignant glioma carries a dismal prognosis, and novel therapies are needed. We examined the feasibility and safety of vaccination with irradiated autologous glioma cells mixed with irradiated GM-K562 cells in patients undergoing craniotomy for recurrent malignant glioma.</jats:p> <jats:p>Experimental Design: We initiated a phase I study examining the safety of 2 doses of GM-K562 cells mixed with autologous cells. Primary endpoints were feasibility and safety. Feasibility was defined as the ability for 60% of enrolled subjects to initiate vaccination. Dose-limiting toxicity was assessed via a 3+3 dose-escalation format, examining irradiated tumor cells mixed with 5 × 106 GM-K562 cells or 1 × 107 GM-K562 cells. Eligibility required a priori indication for resection of a recurrent high-grade glioma. We measured biological activity by measuring delayed type hypersensitivity (DTH) responses, humoral immunity against tumor-associated antigens, and T-lymphocyte activation.</jats:p> <jats:p>Results: Eleven patients were enrolled. Sufficient numbers of autologous tumor cells were harvested in 10 patients, all of whom went on to receive vaccine. There were no dose-limiting toxicities. Vaccination strengthened DTH responses to irradiated autologous tumor cells in most patients, and vigorous humoral responses to tumor-associated angiogenic cytokines were seen as well. T-lymphocyte activation was seen with significantly increased expression of CTLA-4, PD-1, 4-1BB, and OX40 by CD4+ cells and PD-1 and 4-1BB by CD8+ cells. Activation was coupled with vaccine-associated increase in the frequency of regulatory CD4+ T lymphocytes.</jats:p> <jats:p>Conclusions: Vaccination with irradiated autologous tumor cells mixed with GM-K562 cells is feasible, well tolerated, and active in patients with recurrent malignant glioma. Clin Cancer Res; 22(12); 2885–96. ©2016 AACR.</jats:p>
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