Transfer of autologous tumor infiltrating lymphocytes (TIL) to patients with refractory melanoma has shown clinical efficacy in a number of trials. However, extending the clinical benefit to patients with other cancers poses a challenge. Inefficient costimulation in the tumor microenvironment can lead to T cell anergy and exhaustion resulting in poor anti-tumor activity.
View Article and Find Full Text PDFCD8 T cell-mediated recognition of peptide-major histocompatibility complex class I (pMHCI) molecules involves cooperative binding of the T cell receptor (TCR), which confers antigen specificity, and the CD8 coreceptor, which stabilizes the TCR/pMHCI complex. Earlier work has shown that the sensitivity of antigen recognition can be regulated in vitro by altering the strength of the pMHCI/CD8 interaction. Here, we characterized two CD8 variants with moderately enhanced affinities for pMHCI, aiming to boost antigen sensitivity without inducing non-specific activation.
View Article and Find Full Text PDFThis study evaluates the coagulation performance of kenaf protein fractions (KPFs) comprising of albumin (AlbKP), globulin (GloKP), prolamin (ProKP), and glutenin (GluKP), in the treatment of high (500 NTU), medium (150 NTU), and low (30 NTU) turbidity water. Based on preliminary experimental results, the study focused on GloKP due to it outperforming the other kenaf coagulation products (KCPs) in all water types tested. The influence of GloKP, both as a primary coagulant and coagulant aid to aluminum sulfate (AS) on organic matter removal, was examined.
View Article and Find Full Text PDFNonselected autologous tumor-infiltrating lymphocytes (TILs) may provide advantages over other treatments for solid tumors, including checkpoint inhibitor-refractory melanoma. This retrospective analysis reports a single-center experience of nonselected autologous TILs derived from digested tumors for compassionate use treatment of advanced cutaneous melanoma, including after programmed cell death protein 1 (PD-1) inhibition. Patients with histologically confirmed metastatic cutaneous melanoma and no standard-of-care treatment options underwent tumor resection for TIL product manufacturing.
View Article and Find Full Text PDFCD8 T cells are inherently cross-reactive and recognize numerous peptide antigens in the context of a given major histocompatibility complex class I (MHCI) molecule via the clonotypically expressed T cell receptor (TCR). The lineally expressed coreceptor CD8 interacts coordinately with MHCI at a distinct and largely invariant site to slow the TCR/peptide-MHCI (pMHCI) dissociation rate and enhance antigen sensitivity. However, this biological effect is not necessarily uniform, and theoretical models suggest that antigen sensitivity can be modulated in a differential manner by CD8.
View Article and Find Full Text PDFAlthough highway runoff has historically been extensively studied, the increasing complexity of stormwater management means that there are still significant gaps regarding the reduction of soluble metals. The work reported in this paper addresses these challenges by analysing the presence and behaviour of iron, copper and zinc in runoff from junction 24 of the M1 motorway in the UK (peak traffic flow: 30,000 vehicles per hour) and comparing it with other urban sources of metals found in the same catchment (a local brook and sewage treatment works). The sampling site included an interceptor and a treatment lagoon and the event monitoring indicated a trend by which the metals did not change their concentration or particulate soluble proportion immediately, hence showing that pre- and post-storm conditions are important factors when analysing the solubility of metals and their behaviour.
View Article and Find Full Text PDFThe Sustainable Development Goal (SDG) 6.1, established by the United Nations General Assembly in 2015, targets universal and equitable access to safe and affordable drinking water for all by 2030. An essential factor in achieving this goal is the harnessing of "green" coagulants - naturally occurring, environmentally friendly materials which are effective coagulants for use in water treatment, with good availability in developing countries, inherent renewable properties and ease of biodegradation.
View Article and Find Full Text PDFTher Adv Vaccines Immunother
June 2020
With the advent of immunotherapy as a realistic and promising option for cancer treatment, adoptive cellular therapies are gaining significant interest in the clinic. Whilst the recent successes of chimeric antigen receptor T-cell therapies for haematological malignancies are widely known, they have yet to show great success in solid cancers. However, immune cells transduced with T-cell receptors have been shown to traffic to and exert anti-cancer effects on solid tumour cells with some great successes.
View Article and Find Full Text PDFT cells engineered to express antigen-specific T cell receptors (TCRs) are potent therapies for viral infections and cancer. However, efficient identification of clinical candidate TCRs is complicated by the size and complexity of T cell repertoires and the challenges of working with primary T cells. Here we present a high-throughput method to identify TCRs with high functional avidity from diverse human T cell repertoires.
View Article and Find Full Text PDFSci Total Environ
January 2020
There is a need for an inexpensive, reliable and fast monitoring tool to detect contaminants in a short time, for quick mitigation of pollution sources and site remediation, and for characterization of natural dissolved organic matter (DOM). Fluorescence spectroscopy has proven to be an excellent technique in quantifying aquatic DOM, from autochthonous, allochthonous or anthropogenic sources. This paper reviews the advances in in situ fluorescence measurements of DOM and pollutants in various water environments.
View Article and Find Full Text PDFThis study used fluorescence excitation-emission matrices (EEMs) analysis to investigate the characteristics of natural organic matter (NOM) in treated water using okra crude extract (OCE), sabdariffa crude extract (SCE) and kenaf crude extract (KCE) as coagulants. In addition, an assessment of the impact of purified okra protein (POP), purified sabdariffa protein (PSP) and purified kenaf protein (PKP) was undertaken. The performance evaluation of these coagulants in terms of increase or decrease in dissolved organic carbon (DOC) was compared with Peak T fluorescence intensity observed at excitation wavelength 220-230 nm, and emission wavelength 340-360 nm.
View Article and Find Full Text PDFBioresour Technol
October 2018
An Euler-Lagrange CFD model is applied to a full-scale, biogas-mixed anaerobic digester to improve mixing efficiency and improve overall performance. Two quantitative mixing criteria previously adopted in anaerobic digestion (viz., uniformity index and dead volume) are critically assessed for the first time.
View Article and Find Full Text PDFSerial accumulation of mutations to fixation in the SLYNTVATL (SL9) immunodominant, HIV p17 Gag-derived, HLA A2-restricted cytotoxic T lymphocyte epitope produce the SLFNTIAVL triple mutant "ultimate" escape variant. These mutations in solvent-exposed residues are believed to interfere with TCR recognition, although confirmation has awaited structural verification. Here, we solved a TCR co-complex structure with SL9 and the triple escape mutant to determine the mechanism of immune escape in this eminent system.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2017
Tuberculosis (TB), caused by , remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood.
View Article and Find Full Text PDFThe inherent resistance of cancer stem cells (CSCs) to existing therapies has largely hampered the development of effective treatments for advanced malignancy. To help develop novel immunotherapy approaches that efficiently target CSCs, an experimental model allowing reliable distinction of CSCs and non-CSCs was set up to study their interaction with non-MHC-restricted γδ T cells and antigen-specific CD8 T cells. Stable lines with characteristics of breast CSC-like cells were generated from ras-transformed human mammary epithelial (HMLER) cells as confirmed by their CD44 CD24 GD2 phenotype, their mesenchymal morphology in culture and their capacity to form mammospheres under non-adherent conditions, as well as their potent tumorigenicity, self-renewal and differentiation in xenografted mice.
View Article and Find Full Text PDFThe effects of temperature, storage time and water pH on the coagulation performance of okra seed protein in water treatment were assessed. In a jar test experiment, okra salt extract achieved a notable improvement in treatment efficiency with storage time and showed good performance in quality after thermal treatment at 60, 97 and 140 °C temperatures for 6, 4 and 2 hours, respectively. The performance improvement of more than 8% is considered to be due to the denaturation and subsequent removal of coagulation-hindering proteins in okra seed.
View Article and Find Full Text PDFThe CD8 co-receptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR)-binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8 T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude.
View Article and Find Full Text PDFThe growth, breakage and re-growth of flocs formed using crude and purified seed extracts of Okra (OK), Sabdariffa (SB) and Kenaf (KE) as coagulants and coagulant aids was assessed. The results showed floc size increased from 300 μm when aluminium sulphate (AS) was used as a coagulant to between 696 μm and 722 μm with the addition of 50 mg/l of OK, KE and SB crude samples as coagulant aids. Similarly, an increase in floc size was observed when each of the purified proteins was used as coagulant aid at doses of between 0.
View Article and Find Full Text PDFWastewater quality is usually assessed using physical, chemical and microbiological tests, which are not suitable for online monitoring, provide unreliable results, or use hazardous chemicals. Hence, there is an urgent need to find a rapid and effective method for the evaluation of water quality in natural and engineered systems and for providing an early warning of pollution events. Fluorescence spectroscopy has been shown to be a valuable technique to characterize and monitor wastewater in surface waters for tracking sources of pollution, and in treatment works for process control and optimization.
View Article and Find Full Text PDFNowadays, one of the major challenges in the wastewater sector is the successful design and reliable operation of treatment processes, which guarantee high treatment efficiencies to comply with effluent quality criteria, while keeping the investment and operating cost as low as possible. Although conceptual design and process control of activated sludge plants are key to ensuring these goals, they are still based on general empirical guidelines and operators' experience, dominated often by rule of thumb. This review paper discusses the rationale behind the use of Computational Fluid Dynamics (CFD) to model aeration, facilitating enhancement of treatment efficiency and reduction of energy input.
View Article and Find Full Text PDFA novel Euler-Lagrangian (EL) computational fluid dynamics (CFD) finite volume-based model to simulate the gas mixing of sludge for anaerobic digestion is developed and described. Fluid motion is driven by momentum transfer from bubbles to liquid. Model validation is undertaken by assessing the flow field in a labscale model with particle image velocimetry (PIV).
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