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Liam V. Brown Eamonn A. Gaffney Ann Ager Jonathan Wagg Mark C. Coles 《Journal of the Royal Society Interface》2021,18(176)
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. 相似文献
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The present study focuses on the sintering of silicon carbide-based ceramics (SiC) by liquid phase sintering (LPS) followed by characterization of the produced ceramics. AlN/Re2O3 mixtures were used as additives in the LPS process. In the first step, the LPS-SiC materials were produced in a graphite resistance furnace in the form of discs at different temperatures. The conditions with the best results regarding real density and relative density were taken as reference for sintering in the form of prismatic bars. In the second step, these samples were evaluated regarding fracture toughness (KIC), by the Single Edge V Notch Beam – SEVNB – method, and flexural strength. KIC behavior was evaluated according to the depth and curvature radius of the notches. Reliable KIC values were presented when the ceramic displayed a small curvature radius at the notch tip. When the radius was large, it did not maintain the square root singularity of the notch tip. Tests were carried out to determine KIC values in atmospheric air and water. KIC results were lower in water than air, with a decrease ranging between 2.56% and 11.26%. The observations indicated a direct grain size correlation between KIC values and fracture strength of the SiC ceramics. 相似文献
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Scientometrics - The expanding presence of multinational research teams highlights the importance of characterizing the outcomes of international collaboration. Herein, we characterize the... 相似文献
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A new constitutive equation of thermoelasticity for crystals is presented based on the interatomic potential and solid mechanics at finite temperature. Using the new constitutive equation, the calculations for crystal copper and graphene are carried out under different loading paths at different temperatures. The calculated results are in good agreement with those of the previous thermoelasticity constitutive equation based on quantum mechanics, which clearly indicates that our new constitutive equation of thermoelasticity is correct. A lot of comparisons also show that the present theory is more concise and efficient than the previous thermal stress theory in the practical application. 相似文献