Prolonged Persistence of Chimeric Antigen Receptor (CAR) T Cell in Adoptive Cancer Immunotherapy: Challenges and Ways Forward

CAR T cell qualities, such as persistence and functionality play important roles in determining the outcome of cancer immunotherapy. In spite of full functionality, it has been shown that poor persistence of CAR T cells can limit an effective antitumor immune response. Here, we outline specific strategies that can be employed to overcome intrinsic and extrinsic barriers to CAR T cell persistence. We also offer our viewpoint on how growing use of CAR T cells in various cancers may require modifications in the intrinsic and extrinsic survival signals of CAR T cells. We anticipate these amendments will additionally provide the rationales for generation of more persistent, and thereby, more effective CAR T cell treatments. CAR T cell qualities, such as persistence and functionality play important roles in determining the outcome of cancer immunotherapy. In spite of full functionality, it has been shown that poor persistence of CAR T cells can limit an effective antitumor immune response. Here, we outline specific strategies that can be employed to overcome intrinsic and extrinsic barriers to CAR T cell persistence. We also offer our viewpoint on how growing use of CAR T cells in various cancers may require modifications in the intrinsic and extrinsic survival signals of CAR T cells. We anticipate these amendments will additionally provide the rationales for generation of more persistent, and thereby, more effective CAR T cell treatments

Experimental Study on the Phase Equilibrium of Copper Matte and Silica-Saturated FeO x-SiO2-Based Slags in Pyrometallurgical WEEE Processing

The effects of the amphoteric and basic oxides alumina and lime on the phase equilibria of copper matte and silica-saturated slags were investigated at 1300 °C and PSO2 = 0.1 atm in a controlled CO-CO2-SO2-Ar gas atmosphere using a high-temperature isothermal equilibration technique followed by rapid quenching. The equilibrium phase compositions were obtained by Electron Probe X-ray Microanalysis. The relationship between the copper concentration in matte and the oxygen partial pressure, iron, and sulfur in matte was quantified. The pure iron-silicate slag exhibited the highest copper loss in slag, although the addition of alumina and lime decreased its value by approximately a quarter and a half, respectively, at a matte grade of 65 wt pct Cu. In contrast, copper and sulfur were highly distributed in the matte phase, and their deportment to the matte was favored by addition of alumina and lime.Peer reviewe

Equilibrium of Copper Matte and Silica-Saturated Iron Silicate Slags at 1300 °C and PSO2 of 0.5 atm

Experimental study on the phase equilibria between copper matte with silica-saturated iron silicate slags was conducted at 1300 °C and PSO2 = 0.5 atm. The high-temperature isothermal equilibration in silica crucibles under controlled flowing CO-CO2-SO2-Ar was followed by quenching in an ice–water mixture and direct phase composition analyses by an electron probe X-ray microanalyzer. The equilibrium compositions for matte and slag, as well as the distribution coefficients, were displayed as a function of matte grade. The data set obtained at PSO2 = 0.5 atm and the previous study at PSO2 = 0.1 atm by the authors enabled an investigation on the impacts of PSO2 as well as Al2O3 and CaO additions on phase equilibria in the multiphase copper matte smelting system. Thermodynamic calculations using MTDATA software were performed to compare the experimental results with modeling. The present results enrich the fundamental thermodynamic information for the matte/slag/tridymite/gas equilibria in the primary copper smelting process at high PSO2.Peer reviewe