Approaches for the detection and analysis of antidrug antibodies to biopharmaceuticals: A review

Antibody-based therapeutic agents and other biopharmaceuticals are now used in the treatment of many diseases. However, when these biopharmaceuticals are administrated to patients, an immune reaction may occur that can reduce the drug's efficacy and lead to adverse side-effects. The immunogenicity of biopharmaceuticals can be evaluated by detecting and measuring antibodies that have been produced against these drugs, or antidrug antibodies. Methods for antidrug antibody detection and analysis can be important during the selection of a therapeutic approach based on such drugs and is crucial when developing and testing new biopharmaceuticals. This review examines approaches that have been used for antidrug antibody detection, measurement, and characterization. Many of these approaches are based on immunoassays and antigen binding tests, including homogeneous mobility shift assays. Other techniques that have been used for the analysis of antidrug antibodies are capillary electrophoresis, reporter gene assays, surface plasmon resonance spectroscopy, and liquid chromatography-mass spectrometry. The general principles of each approach will be discussed, along with their recent applications with regards to antidrug antibody analysis.     

Multiple intramolecular hydrogen bonds in 2,4‐di‐tert‐butyl‐6‐[N‐(2,6‐diisopropylphenyl)‐P,P‐diphenylphosphorimidoyl]phenol

The title compound, C₃₈H₄₈NOP, isolated from the reaction of (2‐diphenylphosphanyl‐4,6‐di‐tert‐butyl)phenol with 2,6‐diisopropylphenyl azide at 273 K, can act as an N,O‐bidentate ligand. Crystal structure analysis shows a deviation from ideal tetrahedral symmetry around the P atom. The molecule exists as a monomer in the solid state, whose conformation is stabilized via multiple intramolecular hydrogen bonds. Geometric parameters from both experimental and theoretical calculations are compared.     

Environments of ethidium binding to allosteric Dna: II. Accessibility, mobility and mode of binding

DNA binding compounds were previously shown to bind to the right-handed DNA forms and hybrid B-Z forms in a highly cooperative manner and indicate that structural specificity plays a key role in a ligand binding to DNA. In this study, the modes of binding and structural specificity of agents to unusual DNA are examined by a variety of fluorescence techniques (intensity, polarization and quenching, etc.) to explore a reliable method to detect the association environment of ligands to deoxyoligonucleotides initially containing a B-Z junction between the left-handed Z-DNA and right-handed B-DNA. The results of fluorescence energy transfer measurement demonstrated that the ligand molecules bind to the allosterically converted DNA structures by intercalation. In the absence of high-resolution structural data, this fluorescence energy transfer measurement allowed reliable measures and infer the binding environment of ligands to the allosteric DNA structures.     

One-mode model for patterned metal layers inside integrated color pixels

Optimized design of the optical filters inside integrated color pixels (ICPs) for complementary metal-oxide semiconductor image sensors requires analytical models. ICP optical filters consist of subwavelength patterned metal layers. We show that a one-mode model, in which subwavelength gaps in the metal layer are described in terms of single-mode waveguides, suffices to predict the salient features of measured ICP wavelength selectivity. The Airy-like transmittance formula, derived for transverse-electric polarization, predicts an angle-independent cutoff wavelength, which is in good agreement with predictions made with a two-dimensional finite-difference time-domain method.     

Simultaneous acquisition of perfusion and permeability from corrected relaxation rates with dynamic susceptibility contrast dual gradient echo

This study compared two methods, corrected (separation of T(1) and T(2)* effects) and uncorrected, in order to determine the suitability of the perfusion and permeability measures through Delta R(2)* and Delta R(1) analyses. A dynamic susceptibility contrast dual gradient echo (DSC-DGE) was used to image the fixed phantoms and flow phantoms (Sephadex perfusion phantoms and dialyzer phantom for the permeability measurements). The results confirmed that the corrected relaxation rate was linearly proportional to gadolinium-diethyltriamine pentaacetic acid (Gd-DTPA) concentration, whereas the uncorrected relaxation rate did not in the fixed phantom and simulation experiments. For the perfusion measurements, it was found that the correction process was necessary not only for the Delta R(1) time curve but also for the Delta R(2)* time curve analyses. Perfusion could not be measured without correcting the Delta R(2)* time curve. The water volume, which was expressed as the perfusion amount, was found to be closer to the theoretical value when using the corrected Delta R(1) curve in the calculations. However, this may occur in the low concentration of Gd-DTPA in tissue used in this study. For the permeability measurements based on the two-compartment model, the permeability factor (k(ev); e = extravascular, v = vascular) from the outside to the inside of the hollow fibers was greater in the corrected Delta R(1) method than in the uncorrected Delta R(1) method. The differences between the corrected and the uncorrected Delta R(1) values were confirmed by the simulation experiments. In conclusion, this study proposes that the correction for the relaxation rates, Delta R(2)* and Delta R(1), is indispensable in making accurate perfusion and permeability measurements, and that DSC-DGE is a useful method for obtaining information on perfusion and permeability, simultaneously.