Immunogenicity of CAR T cells in cancer therapy

Patient-derived T cells genetically reprogrammed to express CD19-specific chimeric antigen receptors (CARs) have shown remarkable clinical responses and are commercially available for the treatment of patients with certain advanced-stage B cell malignancies. Nonetheless, several trials have revealed pre-existing and/or treatment-induced immune responses to the mouse-derived single-chain variable fragments included in these constructs. These responses might have contributed to both treatment failure and the limited success of redosing strategies observed in some patients. Data from early phase clinical trials suggest that CAR T cells are also associated with immunogenicity-related events in patients with solid tumours. Generally, the clinical implications of anti-CAR immune responses are poorly understood and highly variable between different CAR constructs and malignancies. These observations highlight an urgent need to uncover the mechanisms of immunogenicity in patients receiving CAR T cells and develop validated assays to enable clinical detection. In this Review, we describe the current clinical evidence of anti-CAR immune responses and discuss how new CAR T cell technologies might impact the risk of immunogenicity. We then suggest ways to reduce the risks of anti-CAR immune responses to CAR T cell products that are advancing towards the clinic. Finally, we summarize measures that investigators could consider in order to systematically monitor and better comprehend the possible effects of immunogenicity during trials involving CAR T cells as well as in routine clinical practice

Cetylpyridinium Bromide/Polyvinyl Chloride for Substantially Efficient Capture of Rare Earth Elements from Chloride Solution

A new sorbent cetylpyridinium bromide/polyvinylchloride (CPB/PVC) was prepared and tested to extract rare earth elements (REEs) from their chloride solutions. It was identified by FTIR, TGA, SEM, EDX, and XRD. The impact of various factors such as pH, RE ion initial concentration, contacting time, and dose amount via sorption process was inspected. The optimum pH was 6.0, and the equilibrium contact time was reached at 60 min at 25 °C. The prepared adsorbent (CPB/PVC) uptake capacity was 182.6 mg/g. The adsorption of RE ions onto the CPB/PVC sorbent was found to fit the Langmuir isotherm as well as pseudo-second-order models well. In addition, the thermodynamic parameters of RE ion sorption were found to be exothermic and spontaneous. The desorption of RE ions from the loaded CPB/PVC sorbent was investigated. It was observed that the optimum desorption was achieved at 1.0 M HCl for 60 min contact time at ambient room temperature and a 1:60 solid: liquid phase ratio (S:L). As a result, the prepared CPB/PVC sorbent was recognized as a competitor sorbent for REEs. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.The authors express their gratitude to Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2022R13), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia

Quality of Type 2 Diabetes Management in the States of The Co-Operation Council for the Arab States of the Gulf: A Systematic Review

Type 2 diabetes mellitus is a growing, worldwide public health concern. Recent growth has been particularly dramatic in the states of The Co-operation Council for the Arab States of the Gulf (GCC), and these and other developing economies are at particular risk. We aimed to systematically review the quality of control of type 2 diabetes in the GCC, and the nature and efficacy of interventions. We identified 27 published studies for review. Studies were identified by systematic database searches. Medline and Embase were searched separately (via Dialog and Ovid, respectively; 1950 to July 2010 (Medline), and 1947 to July 2010 (Embase)) on 15/07/2009. The search was updated on 08/07/2010. Terms such as diabetes mellitus, non-insulin-dependent, hyperglycemia, hypertension, hyperlipidemia and Gulf States were used. Our search also included scanning reference lists, contacting experts and hand-searching key journals. Studies were judged against pre-determined inclusion/exclusion criteria, and where suitable for inclusion, data extraction/quality assessment was achieved using a specifically-designed tool. All studies wherein glycaemic-, blood pressure- and/or lipid- control were investigated (clinical and/or process outcomes) were eligible for inclusion. No limitations on publication type, publication status, study design or language of publication were imposed. We found the extent of control to be sub-optimal and relatively poor. Assessment of the efficacy of interventions was difficult due to lack of data, but suggestive that more widespread and controlled trial of secondary prevention strategies may have beneficial outcomes. We found no record of audited implementation of primary preventative strategies and anticipate that controlled trial of such strategies would also be useful

Evidence generation and reproducibility in cell and gene therapy research: A call to action

Stem cells & developmental biolog

Evidence generation and reproducibility in cell and gene therapy research: A call to action.

Editoria

Structural chemistry and thermal properties of some pyrimidine complexes

297-303A few complexes of Fe(III), Co(II), Ni (II) and Cu(II) with uracil, 6-amino uracil , and those with substituted phenylazo-6-amino uracils containing o-methyl, <i style="mso-bidi-font-style: normal">p-carboxy and o-carboxy substituents and 5,5'-diethyl barbituric acid sodium salt have been synthesized and characterized by elemental analysis, magnetic moment and spectral measurements (IR, Uv-vis, ESR). The IR spectra show that uracil exists in keto- enol tautomerism but 6-amino uracil possesses the keto amino-imine structure with some enol form. The iron complexes are with O<i style="mso-bidi-font-style: normal">h geometry, while the cobalt complexes are with different geometries (square planar and Oh). The square planar copper complexes exist in ligand bridged structures. The nickel complexes are of tetrahedral configuration. In general, the azo group is involved in the structural chemistry of the azo complexes. The coordination bond length has been calculated. The thermal properties (TG and DTA) of the compounds and their complexes are measured and discussed and also the thermodynamic parameters are evaluated

Electrolytic Behaviour of Acetylcholine Halides & Perchlorate in Aqueous Solutions

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