Clinical Pathology Selected Abstracts, 1/13

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Serum vitamin D levels in Australian children and adolescents with T1DM

Vitamin D has been associated with the development of autoimmune diseases, such as type 1 diabetes mellitus. Vitamin D is produced in the skin by ultraviolet B radiation and 25-hydroxy vitamin D (25OHD), which is a serum marker for vitamin D concentrations. Some studies have shown an association between low serum 25OHD concentrations and type 1 diabetes mellitus (T1DM), and others have shown an inverse relationship between latitude and the incidence of T1DM. The authors conducted a case-control study in Australia, a sub-tropical environment with abundant sunlight, to determine if children with T1DM have lower serum vitamin D compared to children without T1DM. They studied 56 children with T1DM (14 newly diagnosed) and 46 unrelated control subjects and measured serum 25OHD and 1,25-dihydroxy vitamin D (1,25(OH)2D). They also genotyped in each participant the vitamin D receptor polymorphisms Tqa1, Fok1, and Apa1. These vitamin D receptor polymorphisms were shown in previous studies to influence susceptibility to T1DM. The authors also collected data on the Fitzpatrick skin classification, self-reported daily hours of outdoor exposure, and mean ultraviolet index over a 35-day period. They found that serum 25OHD levels were lower in children with T1DM versus controls. The children with T1DM also had lower self-reported outdoor exposure and mean ultraviolet exposure, and there was no significant difference in distribution of vitamin D receptor polymorphisms. The children with newly diagnosed T1DM had lower 1,25(OH)2D than did controls or children with established diabetes. The authors concluded that low concentrations of vitamin D associated with T1DM are found even in environments with abundant sunlight. They noted, however, that it is unknown if vitamin D is a risk factor or consequence of T1DM.

Greer RM, Portelli SL, Hung BSM, et al. Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes. Pediatr Diabetes. 2012;1–111.

Correspondence: Dr. Ristan M. Greer at r.greer@uq.edu.au

Multi-epitope–pulsed dendritic cell vaccine for newly diagnosed glioblastoma

Glioblastoma multiforme is the most common and most malignant of the primary brain tumors. There has been recent interest in use of immunotherapy, or vaccines targeted against the tumor, as a therapy for glioblastoma multiforme (GBM). The authors reported on an open-label, single-institution, phase-one study that evaluated a new autologous vaccine, ICT-107, for safety and response in patients with GBM or brain-stem glioma. The ICT-107 vaccine targeted antigens that were overexpressed on cancer stem cells and other tumor-specific antigens. These tumor-associated antigens on GBM and cancer stem cells included Her2/neu, TRP-2, AIM-2, gp100, MAGE-1, and IL13Rα2. The vaccine was created using patient dendritic cells obtained through leukapheresis collection. Because dendritic cells are the most potent antigen-presenting cells, they were pulsed with synthetic class-one peptides from the tumor-specific antigens. Following culturing of the dendritic cells with the peptides, the vaccination was give to the patients and immune response was monitored. Study results showed that the 16 newly diagnosed adult GBM patients had a progression-free survival rate of 16.9 months, two-year survival rate of 43.8 percent (95 percent confidence interval [CI], 19.8–66.0), and overall three-year survival rate of 55.6 percent (95 percent CI, 28.6–75.9). Six patients showed no tumor recurrence at 49 to 66 months. Four ICT-107–targeted antigens in the pre-vaccine tumors correlated with prolonged progression-free and overall survival rates. The dendritic cell vaccine did not exhibit toxicity in this study. The authors concluded that this phase-one study of ICT-107 demonstrated the safety, feasibility, and bioactivity of a dendritic cell vaccine for GBM patients. A phase-two randomized controlled trial is underway.

Phuphanich S, Wheeler CJ, Rudnick JD, et al. Phase 1 trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunol Immunother. 2012. doi:10.1007/s00262–012–1319–0.

Correspondence: S. Phuphanich at phuphanich@cshs.org and C. J. Wheeler at wheelerc@cshs.org