A novel electrochemical impedance spectroscopy (EIS) sensor design, based on a standard interdigitated electrode arrangement in which the working electrode consists of gold and the combined counter and reference electrodes of polypyrrole doped with polystyrene sulfonate (PPy:PSS), is evaluated for biosensing applications. The performance is successfully proved by immobilization of a thiolated biotin as a self‐assembled monolayer (SAM), followed by streptavidin and a biotinylated horseradish peroxidase. It is shown that specific binding of biomolecules takes place only at the gold electrode. The binding activities are not influenced by the addition of small amounts of the nonionic surfactant Pluronic F‐68. The immobilization process is monitored online with EIS showing an excellent repeatability of the EIS signals in comparison with Au–Au electrode configuration even after electrode regeneration.
A molecular‐dynamics (MD) simulation study of two heptapeptides containing α‐ and β‐amino acid residues is presented. According to NMR experiments, the two peptides differ in dominant fold when solvated in MeOH: peptide 3 adopts predominantly β‐hairpin‐like conformations, while peptide 8 adopts a 14/15‐helical fold. The MD simulations largely reproduce the experimental data. Application of NOE atomatom distance restraining improves the agreement with experimental data, but reduces the conformational sampling. Peptide 3 shows a variety of conformations, while still agreeing with the NOE and 3J‐coupling data, whereas the conformational ensemble of peptide 8 is dominated by one helical conformation. The results confirm the suitability of the GROMOS 54A7 force field for simulation or structure refinement of mixed α/β‐peptides in MeOH.
Purpose of review Immunotherapy with gene-engineered chimeric antigen receptor (CAR)-T cells has curative potential in advanced malignancies and undergoes a surging preclinical and clinical development. Here, we present a selection of new targets and technologies that illustrate the progress that is being made with the aspiration to make CAR-T cell therapy a universally applicable and effective treatment in cancer medicine. Recent findings There is a rich pipeline of new target antigens for CAR-T cells in hematology and oncology that are rated based on uniformity but also stability of expression on tumor cells under therapeutic pressure. New technologies in CAR-T cell engineering are directed at neutralizing inhibitory ligands and factors in the tumor microenvironment, preventing CAR-T cell exhaustion and enhancing selectivity for tumor cells with ‘smart’ CAR designs. The manufacture of CAR-T cells using virus-free protocols is anticipated to reduce supply-chain complexity and to improve patient access. Summary CD19 CAR-T cell therapy is an approved treatment for B-cell leukemia and -lymphoma and considering the current ‘target and technology’ pipeline, we anticipate that additional CAR-T cell products will accomplish their ‘breakthrough’ and clinical proof-of-concept in other indications in hematology and in oncology. Technologies to enhance therapeutic index and facilitate manufacturing will be key for assuring availability and accessibility of CAR-T cell products and their implementation into routine clinical practice.
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