Characterisation of the new EpCAM-specific antibody HO-3: implications for trifunctional antibody immunotherapy of cancer

Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is frequently overexpressed in a variety of carcinomas. This pan-carcinoma antigen has served as the target for a plethora of immunotherapies. Innovative therapeutic approaches include the use of trifunctional antibodies (trAbs) that recruit and activate different types of immune effector cells at the tumour site. The trAb catumaxomab has dual specificity for EpCAM and CD3. In patients with malignant ascites, catumaxomab significantly increased the paracentesis-free interval, corroborating the high efficacy of this therapeutic antibody. Here, we characterised the monoclonal antibody (mAb) HO-3, that is, the EpCAM-binding arm of catumaxomab. Peptide mapping indicated that HO-3 recognises a discontinuous epitope, having three binding sites in the extracellular region of EpCAM. Studies with glycosylation-deficient mutants showed that mAb HO-3 recognised EpCAM independently of its glycosylation status. High-affinity binding was not only detected for mAb HO-3, but also for the monovalent EpCAM-binding arm of catumaxomab with an excellent KD of 5.6 × 10−10 M. Furthermore, trAb catumaxomab was at least a 1000-fold more effective in eliciting the eradication of tumour cells by effector peripheral blood mononuclear cells compared with mAb HO-3. These findings suggest the great therapeutic potential of trAbs and clearly speak in favour of EpCAM-directed cancer immunotherapies

Vitrification of cesium-loaded crystalline silicotitanate (CST) in the shielded cells melter

Through the Tanks Focus Area, the Savannah River Technology Center (SRTC) and the Oak Ridge National Laboratory participated in a joint project in which supernate waste from the Melton Valley Storage Tanks at Oak Ridge was treated by passage through a crystalline silicotitanate (CST) ion exchange column. CST was designed to sorb Cs- 137, Sr-90 and several other radionuclides from highly alkaline solutions containing large quantities of sodium.2 After demonstrating the effectiveness of CST as an ion exchange medium, ORNL shipped some of the loaded sorbent to SRTC where it was mixed with glass formers and processed in a joule-heated melter within the SRTC Shielded Cells. This report details the results of the melter run, along with the preparations that were required to complete the campaign

Influence of assembly and operation asymmetries on Wendelstein 7-X magnetic field perturbations

Wendelstein 7-X is a modular advanced stellarator realizing a 5-period Helias configuration. An important part of the planned operational plasma scenarios is characterised by a rotational transform ι/2π =1 at the plasma boundary. Such configurations are very sensitive to symmetry breaking perturbations, resonant with the value of the rotational transform at the boundary and violating the toroidal periodicity of the magnetic field. The most critical consequences of magnetic field perturbations are modifications of the island topology, which can result in uneven loads on the divertor targets and affect the plasma performance. In this paper the level of magnetic field perturbations due to possible symmetry distortions under electromagnetic loads is estimated and comparative analysis with previously investigated magnetic field errors is presented

EVALUATION OF THE FAILURE OF A RADIOACTIVE WASTE TRANSFER LINE JACKET

Radioactive wastes are confined in 49 underground storage tanks at the Savannah River Site. The waste is transported between tanks primarily via an underground transfer piping system. Due to the hazardous nature of the waste, the inner core stainless steel pipe is typically surrounded by a carbon steel pipe jacket, which provides secondary containment. Recently several through-wall penetrations were discovered on a segment of one of the jackets. An evaluation was performed to verify the failure mechanism and to estimate the degree of damage that occurred to the pipe segment. Failure analysis of a section of the jacket confirmed that pitting corrosion on the exterior of the pipe led to the through-wall penetration. Ultrasonic measurements on sections of the pipe were utilized to determine the remaining wall thickness in adjacent areas of the pipe. Based on these measurements, the degree of pitting and general corrosion was determined. Pit growth rate models were then developed to estimate the life expectancy of sections of the pipe that had not been excavated. The calculations estimated that the occurrence of through-wall failures in this jacket will begin to increase substantially in 12 years. Given that this pipe segment will be utilized beyond this time, short-term and long-term solutions to this failure were proposed. The short-term solutions focused on the repair or replace decisions that must be made to return the jacket to service as soon as practical. The long-term solutions focused on a broader strategy to address jacket integrity issues in the entire tank farm facility. These solutions included the evaluation of innovative remote inspection and repair techniques