Quantifying the limits of CAR T-cell delivery in mice and men

CAR (Chimeric Antigen Receptor) T cells have demonstrated clinical success for the treatment of multiple lymphomas and leukaemias, but not for various solid tumours, despite promising data from murine models. Lower effective CAR T-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent outcomes. We used anatomical and physiological data for human and rodent circulatory systems to calculate the typical perfusion of healthy and tumour tissues, and estimated the upper limits of immune cell delivery rates across different organs, tumour types and species. Estimated maximum delivery rates were up to 10 000-fold greater in mice than humans yet reported CAR T-cell doses are typically only 10–100-fold lower in mice, suggesting that the effective delivery rates of CAR T cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were found to be consistent with published positron emission tomography data. Results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models, and that lower doses should be tested in mice. We posit that quantitation of species and organ-specific delivery and homing of engineered T cells will be key to unlocking their potential for solid tumours.     

The Indirect Excitons Contribution to the Polarizability of a Dielectric Nanoparticle

Semiconductors - The optical properties of dielectric nanostructures strongly depend on dielectric nanoparticles (NP) polarizability which can take the high values even interacting with...     

Electromechanical analytical model of shape memory alloy based tunable cantilevered piezoelectric energy harvester

International Journal of Mechanics and Materials in Design - The resonant frequency of electromechanical energy harvester should be tuned to ambient frequency so as to maximize the harvester power....     

Radiolabeling,Preparation, and Bioevaluation of 99mTc-Azathioprine as a Potential Targeting Agent for Solid Tumor Imaging

Radiochemistry - Azathioprine, an antitumor agent, was labeled with 99mTc using stannous chloride dihydrate as a reducing agent. Factors such as the amounts of the reducing agent and substrate, pH,...     

Comparative Study of Pseudo-α and Pseudo-β Class Titanium Alloy Sheet Set of High-Tech Properties

Metallurgist - A forming operations for the pseudo-α titanium alloys OT4-1, OT4-1V, OT4V that are used traditionally in aviation and aerospace transport structures, and a new advanced...     

Studying the Effect of Cobalt Doping on Optical and Magnetic Properties of Zinc Oxide Nanoparticles

Silicon - Nano-crystalline powders of Zn1−xCoxO with $\left (0.0\le x\le 0.07 \right )$ have been synthesized by sol-gel method. X-ray diffraction patterns of the prepared samples confirm the...     

Effect of ZnO layer thickness upon optoelectrical properties of NiO/ ZnO heterojunction prepared at room temperature

In this work, p-NiO/n-ZnO heterostructures were successfully prepared at room temperature using RF sputtering technique. The influence of ZnO layer thickness on the performance of the heterojunction was investigated. The deposited ZnO layers have a hexagonal Wurtzite structure with preferable growth orientations along (002) and (103) for thinner films. Increasing the thickness results in more crystallographic orientation randomness. The current–voltage measurements of the realized heterojunctions showed a clear rectifying behavior. The measured ideality factor varies from 2.5 to 1.6 according to the thickness of ZnO layer. The series resistance of the device is enlarged with increasing ZnO thickness. The deduced parameters from the I–V characteristics suggest that 200 nm is the optimal thickness of the ZnO layer according to our experimental conditions. We attribute the relatively better performance of this thickness to achieving reasonable compensation between serial resistance and ideality factor. The best heterojunction was tested and successfully used as a UV detector.     

Improving weld formability by a novel dual-rotation bobbin tool friction stir welding

A novel dual-rotation bobbin tool friction stir welding (DBT-FSW) was developed, in which the upper shoulder (US) and lower shoulder (LS) have different rotational speeds. This process was tried to weld 3.2 mm thick aluminum-lithium alloy sheets. The metallographic analysis and torque measurement were carried out to characterize the weld formability. Experimental results show that compared to conventional bobbin tool friction stir welding, the DBT-FSW has an excellent process stability, and can produce the defect-free joints in a wider range of welding parameters. These can be attributed to the significant improvement of material flow caused by the formation of a staggered layer structure and the unbalanced force between the US and LS during the DBT-FSW process.