655 research outputs found
T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression.
Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of protumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here, we describe the ability of chimeric antigen receptor (CAR)-bearing T cells to recognize human prostate-specific membrane antigen (hPSMA) on endothelial targets in vitro as well as in vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3ζ, CD28, and/or CD137/4-1BB. We found that all anti-hPSMA CAR T cells recognized and eliminated PSMA(+) endothelial targets in vitro, regardless of the signaling domain. T cells bearing the third-generation anti-hPSMA CAR, P28BBζ, were able to recognize and kill primary human endothelial cells isolated from gynecologic cancers. In addition, the P28BBζ CAR T cells mediated regression of hPSMA-expressing vascular neoplasms in mice. Finally, in murine models of ovarian cancers populated by murine vessels expressing hPSMA, the P28BBζ CAR T cells were able to ablate PSMA(+) vessels, cause secondary depletion of tumor cells, and reduce tumor burden. Taken together, these results provide a strong rationale for the use of CAR T cells as agents of tumor vascular disruption, specifically those targeting PSMA. Cancer Immunol Res; 3(1); 68-84. ©2014 AACR
Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment
Introduction: The National Comprehensive Cancer Network guidelines recommend re-challenge with the first-line treatment for relapsed small cell lung cancer (SCLC) with chemotherapy-free interval (CTFI)=180 days. A phase II study (NCT02454972) showed remarkable antitumor activity in SCLC patients treated with lurbinectedin 3.2 mg/m2 1 -h intravenous infusion every 3 weeks as second-line therapy. We report results for the pre-planned subset of patients with CTFI = 180 days.
Material and Methods: Twenty patients aged =18 years with pathologically proven SCLC diagnosis, pretreated with only one prior platinum-containing line, no CNS metastases, and with CTFI = 180 days were evaluated. The primary efficacy endpoint was the overall response rate (ORR) assessed by the Investigators according to RECIST v1.1.
Results: ORR was 60.0 % (95 %CI, 36.1-86.9), with a median duration of response of 5.5 months (95 %CI, 2.9-11.2) and disease control rate of 95.0 % (95 %CI, 75.1-99.9). Median progression-free survival was 4.6 months (95 %CI, 2.6-7.3). With a censoring of 55.0 %, the median overall survival was 16.2 months (95 %CI, 9.6-upper level not reached). Of note, 60.9 % and 27.1 % of patients were alive at 1 and 2 years, respectively. The most common grade 3/4 adverse events and laboratory abnormalities were hematological disorders (neutropenia, 55.0 %; anemia; 10.0 % thrombocytopenia, 10.0 %), fatigue (10.0 %) and increased liver function tests (GGT, 10 %; ALT and AP, 5.0 % each). No febrile neutropenia was reported.
Conclusion: Lurbinectedin is an effective treatment for platinum-sensitive relapsed SCLC, especially in patients with CTFI = 180 days, with acceptable safety and tolerability. These encouraging results suggest that lurbinectedin can be another valuable therapeutic option rather than platinum re-challenge
Heavy quarkonium: progress, puzzles, and opportunities
A golden age for heavy quarkonium physics dawned a decade ago, initiated by
the confluence of exciting advances in quantum chromodynamics (QCD) and an
explosion of related experimental activity. The early years of this period were
chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in
2004, which presented a comprehensive review of the status of the field at that
time and provided specific recommendations for further progress. However, the
broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles
could only be partially anticipated. Since the release of the YR, the BESII
program concluded only to give birth to BESIII; the -factories and CLEO-c
flourished; quarkonium production and polarization measurements at HERA and the
Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the
deconfinement regime. All these experiments leave legacies of quality,
precision, and unsolved mysteries for quarkonium physics, and therefore beg for
continuing investigations. The plethora of newly-found quarkonium-like states
unleashed a flood of theoretical investigations into new forms of matter such
as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the
spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b},
and b\bar{c} bound states have been shown to validate some theoretical
approaches to QCD and highlight lack of quantitative success for others. The
intriguing details of quarkonium suppression in heavy-ion collisions that have
emerged from RHIC have elevated the importance of separating hot- and
cold-nuclear-matter effects in quark-gluon plasma studies. This review
systematically addresses all these matters and concludes by prioritizing
directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K.
Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D.
Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A.
Petrov, P. Robbe, A. Vair
Evidence of Color Coherence Effects in W+jets Events from ppbar Collisions at sqrt(s) = 1.8 TeV
We report the results of a study of color coherence effects in ppbar
collisions based on data collected by the D0 detector during the 1994-1995 run
of the Fermilab Tevatron Collider, at a center of mass energy sqrt(s) = 1.8
TeV. Initial-to-final state color interference effects are studied by examining
particle distribution patterns in events with a W boson and at least one jet.
The data are compared to Monte Carlo simulations with different color coherence
implementations and to an analytic modified-leading-logarithm perturbative
calculation based on the local parton-hadron duality hypothesis.Comment: 13 pages, 6 figures. Submitted to Physics Letters
Measurement of the p-pbar -> Wgamma + X cross section at sqrt(s) = 1.96 TeV and WWgamma anomalous coupling limits
The WWgamma triple gauge boson coupling parameters are studied using p-pbar
-> l nu gamma + X (l = e,mu) events at sqrt(s) = 1.96 TeV. The data were
collected with the DO detector from an integrated luminosity of 162 pb^{-1}
delivered by the Fermilab Tevatron Collider. The cross section times branching
fraction for p-pbar -> W(gamma) + X -> l nu gamma + X with E_T^{gamma} > 8 GeV
and Delta R_{l gamma} > 0.7 is 14.8 +/- 1.6 (stat) +/- 1.0 (syst) +/- 1.0 (lum)
pb. The one-dimensional 95% confidence level limits on anomalous couplings are
-0.88 < Delta kappa_{gamma} < 0.96 and -0.20 < lambda_{gamma} < 0.20.Comment: Submitted to Phys. Rev. D Rapid Communication
Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s} = 1.96 TeV using Kinematic Characteristics of Lepton + Jets Events
We present a measurement of the top quark pair ttbar production cross section
in ppbar collisions at a center-of-mass energy of 1.96 TeV using 230 pb**{-1}
of data collected by the DO detector at the Fermilab Tevatron Collider. We
select events with one charged lepton (electron or muon), large missing
transverse energy, and at least four jets, and extract the ttbar content of the
sample based on the kinematic characteristics of the events. For a top quark
mass of 175 GeV, we measure sigma(ttbar) = 6.7 {+1.4-1.3} (stat) {+1.6- 1.1}
(syst) +/-0.4 (lumi) pb, in good agreement with the standard model prediction.Comment: submitted to Phys.Rev.Let
Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Lepton + Jets Events with Lifetime b-tagging
We present a measurement of the top quark pair () production cross
section () in collisions at TeV
using 230 pb of data collected by the D0 experiment at the Fermilab
Tevatron Collider. We select events with one charged lepton (electron or muon),
missing transverse energy, and jets in the final state. We employ
lifetime-based b-jet identification techniques to further enhance the
purity of the selected sample. For a top quark mass of 175 GeV, we
measure pb, in
agreement with the standard model expectation.Comment: 7 pages, 2 figures, 3 tables Submitted to Phys.Rev.Let
Search for W' bosons decaying to an electron and a neutrino with the D0 detector
This Letter describes the search for a new heavy charged gauge boson W'
decaying into an electron and a neutrino. The data were collected with the D0
detector at the Fermilab Tevatron proton-antiproton Collider at a
center-of-mass energy of 1.96 TeV, and correspond to an integrated luminosity
of about 1 inverse femtobarn. Lacking any significant excess in the data in
comparison with known processes, an upper limit is set on the production cross
section times branching fraction, and a W' boson with mass below 1.00 TeV can
be excluded at the 95% C.L., assuming standard-model-like couplings to
fermions. This result significantly improves upon previous limits, and is the
most stringent to date.Comment: submitted to Phys. Rev. Let
Measurement of the ratios of the Z/G* + >= n jet production cross sections to the total inclusive Z/G* cross section in ppbar collisions at sqrt(s) = 1.96 TeV
We present a study of events with Z bosons and jets produced at the Fermilab
Tevatron Collider in ppbar collisions at a center of mass energy of 1.96 TeV.
The data sample consists of nearly 14,000 Z/G* -> e+e- candidates corresponding
to the integrated luminosity of 0.4 fb-1 collected using the D0 detector.
Ratios of the Z/G* + >= n jet cross sections to the total inclusive Z/G* cross
section have been measured for n = 1 to 4 jet events. Our measurements are
found to be in good agreement with a next-to-leading order QCD calculation and
with a tree-level QCD prediction with parton shower simulation and
hadronization.Comment: 7 pages, 2 figures, slightly modified, submitted to Phys. Lett.
Measurement of the Isolated Photon Cross Section in p-pbar Collisions at sqrt{s}=1.96 TeV
The cross section for the inclusive production of isolated photons has been
measured in p anti-p collisions at sqrt{s}=1.96 TeV with the D0 detector at the
Fermilab Tevatron Collider. The photons span transverse momenta 23 to 300 GeV
and have pseudorapidity |eta|<0.9. The cross section is compared with the
results from two next-to-leading order perturbative QCD calculations. The
theoretical predictions agree with the measurement within uncertainties.Comment: 7 pages, 5 figures, submitted to Phys.Lett.
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