BACKGROUND AIMS: Dendritic cell (DC)-based vaccination targeting tumor-associated antigens is an attractive approach to overcoming the limitations of current treatments for malignant gliomas (MG). Interleukin-13 receptor α2 chain (IL-13Rα2) is a promising target because of its abundant and specific expression in MG. We conducted a phase I trial of DC vaccination in patients with recurrent MG using two IL-13Rα2-derived peptides restricted to HLA-A*0201 and -A*2402. The objective was to evaluate the safety and clinical and immunologic responses. METHODS: Eight recurrent MG patients were enrolled. DC were generated from peripheral blood and pulsed with HLA-matched peptide; 1 × 10(7) DC were administered every 2 weeks for a maximum of six immunizations. The T-cell response in peripheral blood was evaluated by tetramer and ELISPOT assays in HLA-A*2402 patients. RESULTS: All enrolled patients except one completed at least four DC vaccinations. No severe adverse events were observed. A positive T-cell response was detected in two out of three evaluable HLA-A*2402 patients. One patient achieved stable disease for 16 months and another patient showed a dramatic regression for one lesion for 4 months. CONCLUSIONS: The regimen was feasible and safe, and the HLA-A*24-restricted peptide exhibited a capacity to induce immune responses. These results warrant further studies to evaluate whether add-on regimens to post-operative chemoradiotherapy delays recurrence in newly diagnosed MG patients.
BACKGROUND AIMS: Dendritic cell (DC)-based vaccination targeting tumor-associated antigens is an attractive approach to overcoming the limitations of current treatments for malignant gliomas (MG). Interleukin-13 receptor α2 chain (IL-13Rα2) is a promising target because of its abundant and specific expression in MG. We conducted a phase I trial of DC vaccination in patients with recurrent MG using two IL-13Rα2-derived peptides restricted to HLA-A*0201 and -A*2402. The objective was to evaluate the safety and clinical and immunologic responses. METHODS: Eight recurrent MG patients were enrolled. DC were generated from peripheral blood and pulsed with HLA-matched peptide; 1 × 10(7) DC were administered every 2 weeks for a maximum of six immunizations. The T-cell response in peripheral blood was evaluated by tetramer and ELISPOT assays in HLA-A*2402 patients. RESULTS: All enrolled patients except one completed at least four DC vaccinations. No severe adverse events were observed. A positive T-cell response was detected in two out of three evaluable HLA-A*2402 patients. One patient achieved stable disease for 16 months and another patient showed a dramatic regression for one lesion for 4 months. CONCLUSIONS: The regimen was feasible and safe, and the HLA-A*24-restricted peptide exhibited a capacity to induce immune responses. These results warrant further studies to evaluate whether add-on regimens to post-operative chemoradiotherapy delays recurrence in newly diagnosed MG patients.
Authors: Tiffany R Hodges; Sherise D Ferguson; Hillary G Caruso; Gary Kohanbash; Shouhao Zhou; Timothy F Cloughesy; Mitchel S Berger; George H Poste; Mustafa Khasraw; Sujuan Ba; Tao Jiang; Tom Mikkelson; W K Alfred Yung; John F de Groot; Howard Fine; Lewis C Cantley; Ingo K Mellinghoff; Duane A Mitchell; Hideho Okada; Amy B Heimberger Journal: Oncoimmunology Date: 2016-02-18 Impact factor: 8.110
Authors: Vidyalakshmi Chandramohan; Duane A Mitchell; Laura A Johnson; John H Sampson; Darell D Bigner Journal: Future Oncol Date: 2013-07 Impact factor: 3.404
Authors: Christine E Brown; Behnam Badie; Michael E Barish; Lihong Weng; Julie R Ostberg; Wen-Chung Chang; Araceli Naranjo; Renate Starr; Jamie Wagner; Christine Wright; Yubo Zhai; James R Bading; Julie A Ressler; Jana Portnow; Massimo D'Apuzzo; Stephen J Forman; Michael C Jensen Journal: Clin Cancer Res Date: 2015-06-09 Impact factor: 12.531