T cells engineered to express chimeric antigen receptors (CAR-T cells) have shown impressive clinical efficacy in the treatment of B cell malignancies. However, the development of CAR-T cell ...therapies for solid tumors is hampered by the lack of truly tumor-specific antigens and poor control over T cell activity. Here we present an avidity-controlled CAR (AvidCAR) platform with inducible and logic control functions. The key is the combination of (i) an improved CAR design which enables controlled CAR dimerization and (ii) a significant reduction of antigen-binding affinities to introduce dependence on bivalent interaction, i.e. avidity. The potential and versatility of the AvidCAR platform is exemplified by designing ON-switch CARs, which can be regulated with a clinically applied drug, and AND-gate CARs specifically recognizing combinations of two antigens. Thus, we expect that AvidCARs will be a highly valuable platform for the development of controllable CAR therapies with improved tumor specificity.
Reported here are transverse single-spin asymmetries (AN) in the production of charged hadrons as a function of transverse momentum (pT) and Feynman-x (xF) in polarized p↑ + p, p↑ + Al, and p↑ + Au ...collisions at $\sqrt{^SNN}$ = 200 GeV. The measurements have been performed at forward and backward rapidity (1.4 < |η| < 2.4) over the range of 1.5 GeV /c < pT < 7.0 GeV /c and 0.04 < |xF| < 0.2. A nonzero asymmetry is observed for positively charged hadrons at forward rapidity (xF > 0) in p↑ + p collisions, whereas the p↑ + Al and p↑ + Au results show smaller asymmetries. This finding provides new opportunities to investigate the origin of transverse single-spin asymmetries and a tool to study nuclear effects in p + A collisions.
Presented are the first measurements of the transverse single-spin asymmetries ($A_N$) for neutral pions and eta mesons in $\textit{p}$ + Au and $\textit{p}$ + Al collisions at $\sqrt{s_{NN}}$ = 200 ...GeV in the pseudorapidity range |$\textit{η}$| < 0.35 with the PHENIX detector at the Relativistic Heavy Ion Collider. The asymmetries are consistent with zero, similar to those for midrapidity neutral pions and eta mesons produced in $\textit{p}$ + $\textit{p}$ collisions. These measurements show no evidence of additional effects that could potentially arise from the more complex partonic environment present in proton-nucleus collisions.
Polarized proton-proton collisions provide leading-order access to gluons, presenting an opportunity to constrain gluon spin-momentum correlations within transversely polarized protons and enhance ...our understanding of the three-dimensional structure of the proton. Midrapidity open-heavy-flavor production at $\sqrt{s}$ = 200 GeV is dominated by gluon-gluon fusion, providing heightened sensitivity to gluon dynamics relative to other production channels. Transverse single-spin asymmetries of positrons and electrons from heavy-flavor hadron decays are measured at midrapidity using the PHENIX detector at the Relativistic Heavy Ion Collider. These charge-separated measurements are sensitive to gluon correlators that can in principle be related to gluon orbital angular momentum via model calculations. Explicit constraints on gluon correlators are extracted for two separate models, one of which had not been constrained previously.
The cross section and transverse single-spin asymmetries of μ− and μ+ from open heavy-flavor decays in polarized p+p collisions at s=200 GeV were measured by the PHENIX experiment during 2012 at the ...Relativistic Heavy Ion Collider. Because heavy-flavor production is dominated by gluon-gluon interactions at s=200 GeV, these measurements offer a unique opportunity to obtain information on the trigluon correlation functions. The measurements are performed at forward and backward rapidity (1.4<|y|<2.0) over the transverse momentum range of 1.25<pT<7 GeV/c for the cross section and 1.25<pT<5 GeV/c for the asymmetry measurements. The obtained cross section is compared to a fixed-order-plus-next-to-leading-log perturbative-quantum-chromodynamics calculation. The asymmetry results are consistent with zero within uncertainties, and a model calculation based on twist-3 three-gluon correlations agrees with the data.
CAR T cells have generated great excitement due to their remarkable clinical response rates in selected hematologic malignancies. However, these engineered immune cells are living drugs which are ...hard to control after administration.INTRODUCTIONCAR T cells have generated great excitement due to their remarkable clinical response rates in selected hematologic malignancies. However, these engineered immune cells are living drugs which are hard to control after administration.We discuss small molecule-regulated switch systems which can potentially be used to control CAR T cell function within the patient, as well as the most important obstacles in the CAR T cell field, which might be overcome with those switch systems.AREAS COVEREDWe discuss small molecule-regulated switch systems which can potentially be used to control CAR T cell function within the patient, as well as the most important obstacles in the CAR T cell field, which might be overcome with those switch systems.There is an urgent need to develop advanced switch systems. Once available, we expect that they will open up new avenues for future CAR T cell generations.EXPERT OPINIONThere is an urgent need to develop advanced switch systems. Once available, we expect that they will open up new avenues for future CAR T cell generations.
In 2015, the PHENIX collaboration has measured very forward (η > 6.8) single spin asymmetries of inclusive neutrons in transversely polarized proton-proton and proton-nucleus collisions at a center ...of mass energy of 200 GeV. A previous publication from this dataset concentrated on the nuclear dependence of such asymmetries. In this measurement the explicit transverse momentum dependence of inclusive neutron single spin asymmetries for proton-proton collisions is extracted using a bootstrapping unfolding technique on the transverse momenta. This explicit transverse momentum dependence will help improve the understanding of the mechanisms that create these asymmetries.
The PHENIX experiment at the Relativistic Heavy Ion Collider has measured the differential cross section, mean transverse momentum, mean transverse momentum squared of inclusive J/ψ, and cross ...section ratio of ψ(2S) to J/ψ at forward rapidity in p + p collisions at √s = 510 GeV via the dimuon decay channel. Comparison is made to inclusive J/ψ cross sections measured at √s = 200 GeV and 2.76–13 TeV. The result is also compared to leading-order nonrelativistic QCD calculations coupled to a color-glass-condensate description of the low-x gluons in the proton at low transverse momentum (pT) and to next-to-leading order nonrelativistic QCD calculations for the rest of the pTrange. These calculations overestimate the data at low pT. While consistent with the data within uncertainties above ≈ 3 GeV/c, the calculations are systematically below the data. The total cross section times the branching ratio is BR dσJ/ψpp/dy(1.2 < |y| < 2.2, 0 < pT< 10 GeV/c) = 54.3 ± 0.5 (stat) ± 5.5 (syst) nb.
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