Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma
This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor-associated antigens (TAA) expressed on gliomas and overexpressed in their cancer stem cell population (ICT-107).
TAA epitopes included HER2, TRP-2, gp100, MAGE-1, IL13Rα2, and AIM-2. HLA-A1- and/or HLA-A2-positive patients with glioblastoma (GBM) were eligible. Mononuclear cells from leukapheresis were differentiated into dendritic cells, pulsed with TAA peptides, and administered intradermally three times at two-week intervals.
Twenty-one patients were enrolled with 17 newly diagnosed (ND-GBM) and three recurrent GBM patients and one brainstem glioma. Immune response data on 15 newly diagnosed patients showed 33 % responders. TAA expression by qRT-PCR from fresh-frozen tumor samples showed all patient tumors expressed at least three TAA, with 75 % expressing all six. Correlations of increased PFS and OS with quantitative expression of MAGE1 and AIM-2 were observed, and a trend for longer survival was observed with gp100 and HER2 antigens. Target antigens gp100, HER1, and IL13Rα2 were downregulated in recurrent tumors from 4 HLA-A2+ patients. A decrease in or absence of CD133 expression was seen in five patients who underwent a second resection. At a median follow-up of 40.1 months, six of 16 ND-GBM patients showed no evidence of tumor recurrence. Median PFS in newly diagnosed patients was 16.9 months, and median OS was 38.4 months.
Expression of four ICT-107 targeted antigens in the pre-vaccine tumors correlated with prolonged overall survival and PFS in ND-GBM patients. The goal of targeting tumor antigens highly expressed on glioblastoma cancer stem cells is supported by the observation of decreased or absent CD133 expression in the recurrent areas of gadolinium-enhanced tumors.
- Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Cancer Immunology, Immunotherapy
Volume 62, Issue 1 , pp 125-135
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- Dendritic cell immunotherapy
- Cancer stem cells
- Cancer vaccine
- Industry Sectors
- Author Affiliations
- 1. Neuro-Oncology Program, Department of Neurosurgery and Neurology, Cedars-Sinai Medical Center, 8631 W. 3rd Street Suite 410 E, Los Angeles, CA, 90048, USA
- 3. Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Road, Davis 2097, Los Angeles, CA, 90048, USA
- 5. Neuro-Oncology Program, Department of Neurosurgery, Cedars-Sinai Medical Center, 8631 W. 3rd Street Suite 800 E, Los Angeles, CA, 90048, USA
- 4. Department of Pathology, Cedars-Sinai Medical Center, 8700 Beverly Blvd. room 8725, Los Angeles, CA, 90048, USA
- 2. ImmunoCellular Therapeutics Ltd., Woodland Hills, CA, USA