In Vivo Fate and Activity of Second- versus Third-Generation CD19-Specific CAR-T Cells in B Cell Non-Hodgkin's Lymphomas

Second-generation (2G) chimeric antigen receptors (CARs) targeting CD19 are highly active against B cell malignancies, but it is unknown whether any of the costimulatory domains incorporated in the CAR have superior activity to others. Because CD28 and 4-1BB signaling activate different pathways, combining them in a single third-generation (3G) CAR may overcome the limitations of each individual costimulatory domain. We designed a clinical trial in which two autologous CD19-specific CAR-transduced T cell products (CD19.CARTs), 2G (with CD28 only) and 3G (CD28 and 4-1BB), were infused simultaneously in 16 patients with relapsed or refractory non-Hodgkin's lymphoma. 3G CD19.CARTs had superior expansion and longer persistence than 2G CD19.CARTs. This difference was most striking in the five patients with low disease burden and few circulating normal B cells, in whom 2G CD19.CARTs had limited expansion and persistence and correspondingly reduced area under the curve. Of the 11 patients with measurable disease, three achieved complete responses and three had partial responses. Cytokine release syndrome occurred in six patients but was mild, and no patient required anti-IL-6 therapy. Hence, 3G CD19.CARTs combining 4-1BB with CD28 produce superior CART expansion and may be of particular value when treating low disease burden in patients whose normal B cells are depleted by prior therapy. CD19.CAR-T cells are highly active against B cell malignancies, but the optimal CAR structure is controversial. Ramos et al. show that combining 4-1BB and CD28 endodomains produces superior CD19-CAR-T cell expansion and persistence compared to CD28 alone and that these cells are clinically effective and safe in aggressive lymphomas

Search for charged Higgs bosons produced in top-quark decays or in association with top quarks and decaying via H±→τ±ντ in 13 TeV pp collisions with the ATLAS detector

Charged Higgs bosons produced either in top-quark decays or in association with a top quark, subsequently decaying via H±→τ±ντ, are searched for in 140  fb−1 of proton-proton collision data at s=13  TeV recorded with the ATLAS detector. Depending on whether the top quark is produced together with the H± decays hadronically or semileptonically, the search targets τ+jets or τ+lepton final states, in both cases with a τ-lepton decaying into a neutrino and hadrons. No significant excess over the Standard Model background expectation is observed. For the mass range of 80≤mH±≤3000  GeV, upper limits at 95% confidence level are set on the production cross section of the charged Higgs boson times the branching fraction B(H±→τ±ντ) in the range 4.5 pb–0.4 fb. In the mass range 80–160 GeV, assuming the Standard Model cross section for tt¯ production, this corresponds to upper limits between 0.27% and 0.02% on B(t→bH±)×B(H±→τ±ντ).</jats:p

Improved reconstruction of highly boosted τ -lepton pairs in the τ τ → (μνμντ )(hadrons + ντ ) decay channels with the ATLAS detector

This paper presents a new τ -lepton reconstruction and identification procedure at the ATLAS detector at the Large Hadron Collider, which leads to significantly improved performance in the case of physics processes where a highly boosted pair of τ -leptons is produced and one τ -lepton decays into a muon and two neutrinos (τμ), and the other decays into hadrons and one neutrino (τhad). By removing the muon information from the signals used for reconstruction and identification of the τhad candidate in the boosted pair, the efficiency is raised to the level expected for an isolated τhad. The new procedure is validated by selecting a sample of highly boosted Z → τμτhad candidates from the data sample of 140 fb−1 of proton–proton collisions at 13 TeV recorded with the ATLAS detector. Good agreement is found between data and simulation predictions in both the Z → τμτhad signal region and in a background validation region. The results presented in this paper demonstrate the effectiveness of the τhad reconstruction with muon removal in enhancing the signal sensitivity of the boosted τμτhad channel at the ATLAS detector

Reconstruction and identification of pairs of collimated τ-leptons decaying hadronically using sqrt{s}=13 TeV pp collision data with the ATLAS detector

This paper describes an algorithm for reconstructing and identifying a highly collimated hadronically decaying τ -lepton pair with low transverse momentum. When two τ -leptons are highly collimated, their visible decay products might overlap, degrading the reconstruction performance for each of the τ -leptons. A dedicated treatment attempting to tag the τ -lepton pair as a single object is required. The reconstruction algorithm is based on a large radius jet and its associated two leading subjets, and the identification uses a boosted decision tree to discriminate between signatures from τ +τ − systems and those arising from QCD jets. The efficiency of the identification algorithm is measured in Zγ events using proton–proton collision data at √s = 13 TeV collected by the ATLAS experiment at the Large Hadron Collider between 2015 and 2018, corresponding to an integrated luminosity of 139 fb−1. The resulting data-to-simulation scale factors are close to unity with uncertainties ranging from 26 to 37%

Cross-section measurements for the production of a W-boson in association with high-transverse-momentum jets in pp collisions at √s = 13 TeV with the ATLAS detector

A set of measurements for the production of a W-boson in association with high-transverse-momentum jets is presented using 140 fb−1 of proton–proton collision data at a centre-of-mass energy of √s = 13 TeV collected by the ATLAS detector at the LHC. The measurements are performed in final states in which the W-boson decays into an electron or muon plus a neutrino and is produced in association with jets with pT > 30 GeV, where the leading jet has pT > 500 GeV. The angular separation between the lepton and the closest jet with pT > 100 GeV is measured and used to define a collinear phase space, wherein measurements of kinematic properties of the W-boson and the associated jet are performed. The collinear phase space is populated by dijet events radiating a W-boson and events with a W-boson produced in association with several jets and it serves as an excellent data sample to probe higher-order theoretical predictions. Measured differential distributions are compared with predictions from state-of-the-art next-to-leading order multi-leg merged Monte Carlo event generators and a fixedorder calculation of the W +1-jet process computed at nextto-next-to-leading order in the strong coupling constant

Search for supersymmetry using vector boson fusion signatures and missing transverse momentum in pp collisions at √s = 13 TeV with the ATLAS detector

This paper presents a search for supersymmetric particles in models with highly compressed mass spectra, in events consistent with being produced through vector boson fusion. The search uses 140 fb−1 of proton-proton collision data at √s = 13 TeV collected by the ATLAS experiment at the Large Hadron Collider. Events containing at least two jets with a large gap in pseudorapidity, large missing transverse momentum, and no reconstructed leptons are selected. A boosted decision tree is used to separate events consistent with the production of supersymmetric particles from those due to Standard Model backgrounds. The data are found to be consistent with Standard Model predictions. The results are interpreted using simplified models of R-parity-conserving supersymmetry in which the lightest supersymmetric partner is a bino-like neutralino with a mass similar to that of the lightest chargino and second-to-lightest neutralino, both of which are wino-like. Lower limits at 95% confidence level on the masses of next-to-lightest supersymmetric partners in this simplified model are established between 117 and 120 GeV when the lightest supersymmetric partners are within 1 GeV in mass

Measurement of double-differential charged-current Drell-Yan cross-sections at high transverse masses in pp collisions at √s = 13 TeV with the ATLAS detector

This paper presents a first measurement of the cross-section for the charged-current Drell-Yan process $pp\rightarrow W^{\pm} \rightarrow \ell^{\pm} \nu$ above the resonance region, where $\ell$ is an electron or muon. The measurement is performed for transverse masses, $m_{\text{T}}^{\text{W}}$, between 200 GeV and 5000 GeV, using a sample of 140 fb$^{-1}$ of $pp$ collision data at a centre-of-mass energy of $\sqrt{s}$ = 13 TeV collected by the ATLAS detector at the LHC during 2015-2018. The data are presented single differentially in transverse mass and double differentially in transverse mass and absolute lepton pseudorapidity. A test of lepton flavour universality shows no significant deviations from the Standard Model. The electron and muon channel measurements are combined to achieve a total experimental precision of 3% at low $m_{\text{T}}^{\text{W}}$. The single- and double differential $W$-boson charge asymmetries are evaluated from the measurements. A comparison to next-to-next-to-leading-order perturbative QCD predictions using several recent parton distribution functions and including next-to-leading-order electroweak effects indicates the potential of the data to constrain parton distribution functions. The data are also used to constrain four fermion operators in the Standard Model Effective Field Theory formalism, in particular the lepton-quark operator Wilson coefficient $c_{\ell q}^{(3)}.

Search for long-lived charged particles using large specific ionisation loss and time of flight in 140 fb−1 of pp collisions at = 13 TeV with the ATLAS detector

This paper presents a search for massive, charged, long-lived particles with the ATLAS detector at the Large Hadron Collider using an integrated luminosity of 140 f b−1 of proton-proton collisions at √ s = 13 TeV. These particles are expected to move signifcantly slower than the speed of light. In this paper, two signal regions provide complementary sensitivity. In one region, events are selected with at least one charged-particle track with high transverse momentum, large specifc ionisation measured in the pixel detector, and time of fight to the hadronic calorimeter inconsistent with the speed of light. In the other region, events are selected with at least two tracks of opposite charge which both have a high transverse momentum and an anomalously large specifc ionisation. The search is sensitive to particles with lifetimes greater than about 3 ns with masses ranging from 200 GeV to 3 TeV. The results are interpreted to set constraints on the supersymmetric pair production of long-lived R-hadrons, charginos and staus, with mass limits extending beyond those from previous searches in broad ranges of lifetime