Highly Efficient Elimination of Colorectal Tumor-Initiating Cells by an EpCAM/CD3-Bispecific Antibody Engaging Human T Cells

With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs) are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Measurement of the B0s→μ+μ− Branching Fraction and Effective Lifetime and Search for B0→μ+μ− Decays

A search for the rare decays Bs0→μ+μ- and B0→μ+μ- is performed at the LHCb experiment using data collected in pp collisions corresponding to a total integrated luminosity of 4.4  fb-1. An excess of Bs0→μ+μ- decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be B(Bs0→μ+μ-)=(3.0±0.6-0.2+0.3)×10-9, where the first uncertainty is statistical and the second systematic. The first measurement of the Bs0→μ+μ- effective lifetime, τ(Bs0→μ+μ-)=2.04±0.44±0.05  ps, is reported. No significant excess of B0→μ+μ- decays is found, and a 95% confidence level upper limit, B(B0→μ+μ-)<3.4×10-10, is determined. All results are in agreement with the standard model expectations.A search for the rare decays $B^0_s\to\mu^+\mu^-$ and $B^0\to\mu^+\mu^-$ is performed at the LHCb experiment using data collected in $pp$ collisions corresponding to a total integrated luminosity of 4.4 fb$^{-1}$. An excess of $B^0_s\to\mu^+\mu^-$ decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be ${\cal B}(B^0_s\to\mu^+\mu^-)=\left(3.0\pm 0.6^{+0.3}_{-0.2}\right)\times 10^{-9}$, where the first uncertainty is statistical and the second systematic. The first measurement of the $B^0_s\to\mu^+\mu^-$ effective lifetime, $\tau(B^0_s\to\mu^+\mu^-)=2.04\pm 0.44\pm 0.05$ ps, is reported. No significant excess of $B^0\to\mu^+\mu^-$ decays is found and a 95 % confidence level upper limit, ${\cal B}(B^0\to\mu^+\mu^-)<3.4\times 10^{-10}$, is determined. All results are in agreement with the Standard Model expectations

Measurement of CP violation parameters and polarisation fractions in Bs0→J/ψK‾∗0 {\mathrm{B}}_{\mathrm{s}}^0\to \mathrm{J}/\psi {\overline{\mathrm{K}}}^{\ast 0} decays

The first measurement of ${C\!P}$ asymmetries in the decay ${B_s^0\to J/\psi \overline{K}^{*}(892)^{0}}$ and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of $3.0\,fb^{-1}$ of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of $7$ and $8\,\mathrm{TeV}$. Together with constraints from ${B^0\to J/\psi \rho^0}$, the results are used to constrain additional contributions due to penguin diagrams in the ${C\!P}$-violating phase ${{\phi}_{s}}$, measured through ${B_s^0}$ decays to charmonium.The first measurement of CP asymmetries in the decay ${B}_s^0\to J/\psi {\overline{\mathrm{K}}}^{\ast }{(892)}^0$ and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of 3.0 fb^{−}^{1} of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Together with constraints from B$^{0}$ → J/ψ ρ$^{0}$, the results are used to constrain additional contributions due to penguin diagrams in the CP -violating phase ϕ$_{s}$ , measured through B$_{s}^{0}$ decays to charmonium.The first measurement of ${C\!P}$ asymmetries in the decay ${B_s^0\to J/\psi \overline{K}^{*}(892)^{0}}$ and an updated measurement of its branching fraction and polarisation fractions are presented. The results are obtained using data corresponding to an integrated luminosity of $3.0\,fb^{-1}$ of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of $7$ and $8\,\mathrm{TeV}$. Together with constraints from ${B^0\to J/\psi \rho^0}$, the results are used to constrain additional contributions due to penguin diagrams in the ${C\!P}$-violating phase ${{\phi}_{s}}$, measured through ${B_s^0}$ decays to charmonium

Measurement of the J/ψ pair production cross-section in pp collisions at s=13 \sqrt{s}=13 TeV

The production cross-section of J/ψ pairs is measured using a data sample of pp collisions collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=13$ TeV, corresponding to an integrated luminosity of 279 ±11 pb$^{−1}$. The measurement is performed for J/ψ mesons with a transverse momentum of less than 10 GeV/c in the rapidity range 2.0 < y < 4.5. The production cross-section is measured to be 15.2 ± 1.0 ± 0.9 nb. The first uncertainty is statistical, and the second is systematic. The differential cross-sections as functions of several kinematic variables of the J/ψ pair are measured and compared to theoretical predictions.The production cross-section of $J/\psi$ pairs is measured using a data sample of $pp$ collisions collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s} = 13 \,{\mathrm{TeV}}$, corresponding to an integrated luminosity of $279 \pm 11 \,{\mathrm{pb^{-1}}}$. The measurement is performed for $J/\psi$ mesons with a transverse momentum of less than $10 \,{\mathrm{GeV}}/c$ in the rapidity range $2.0<y<4.5$. The production cross-section is measured to be $15.2 \pm 1.0 \pm 0.9 \,{\mathrm{nb}}$. The first uncertainty is statistical, and the second is systematic. The differential cross-sections as functions of several kinematic variables of the $J/\psi$ pair are measured and compared to theoretical predictions

Measurement of forward W→eνW\to e\nu production in pppp collisions at s=8 \sqrt{s}=8\,TeV

A measurement of the cross-section for $W \to e\nu$ production in $pp$ collisions is presented using data corresponding to an integrated luminosity of $2\,$fb$^{-1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8\,$TeV. The electrons are required to have more than $20\,$GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive $W$ production cross-sections, where the $W$ decays to $e\nu$, are measured to be \begin{align*} \begin{split} \sigma_{W^{+} \to e^{+}\nu_{e}}&=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\,\mathrm{pb},\\ \sigma_{W^{-} \to e^{-}\bar{\nu}_{e}}&=\,\,\,809.0\pm 1.9\pm 18.1\pm\,\,\,7.0\pm \phantom{0}9.4\,\mathrm{pb}, \end{split} \end{align*} where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination. Differential cross-sections as a function of the electron pseudorapidity are measured. The $W^{+}/W^{-}$ cross-section ratio and production charge asymmetry are also reported. Results are compared with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics. Finally, in a precise test of lepton universality, the ratio of $W$ boson branching fractions is determined to be \begin{align*} \begin{split} \mathcal{B}(W \to e\nu)/\mathcal{B}(W \to \mu\nu)=1.020\pm 0.002\pm 0.019, \end{split} \end{align*} where the first uncertainty is statistical and the second is systematic.A measurement of the cross-section for $W \to e\nu$ production in $pp$ collisions is presented using data corresponding to an integrated luminosity of $2\,$fb$^{-1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8\,$TeV. The electrons are required to have more than $20\,$GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive $W$ production cross-sections, where the $W$ decays to $e\nu$, are measured to be \begin{equation*} \sigma_{W^{+} \to e^{+}\nu_{e}}=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\,\mathrm{pb}, \end{equation*} \begin{equation*} \sigma_{W^{-} \to e^{-}\bar{\nu}_{e}}=\,\,\,809.0\pm 1.9\pm 18.1\pm\,\,\,7.0\pm \phantom{0}9.4\,\mathrm{pb}, \end{equation*} where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination. Differential cross-sections as a function of the electron pseudorapidity are measured. The $W^{+}/W^{-}$ cross-section ratio and production charge asymmetry are also reported. Results are compared with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics. Finally, in a precise test of lepton universality, the ratio of $W$ boson branching fractions is determined to be \begin{equation*} \mathcal{B}(W \to e\nu)/\mathcal{B}(W \to \mu\nu)=1.020\pm 0.002\pm 0.019, \end{equation*} where the first uncertainty is statistical and the second is systematic.A measurement of the cross-section for W → eν production in pp collisions is presented using data corresponding to an integrated luminosity of 2 fb$^{−1}$ collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=8$ TeV. The electrons are required to have more than 20 GeV of transverse momentum and to lie between 2.00 and 4.25 in pseudorapidity. The inclusive W production cross-sections, where the W decays to eν, are measured to be ${\sigma}_{W^{+}\to {e}^{+}{\nu}_e}=1124.4\pm 2.1\pm 21.5\pm 11.2\pm 13.0\kern0.5em \mathrm{p}\mathrm{b},$ ${\sigma}_{W^{-}\to {e}^{-}{\overline{\nu}}_e}=809.0\pm 1.9\pm 18.1\pm \kern0.5em 7.0\pm \kern0.5em 9.4\,\mathrm{p}\mathrm{b},$ where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination

Measurements of prompt charm production cross-sections in pp collisions at s=5 \sqrt{s}=5 TeV

Production cross-sections of prompt charm mesons are measured using data from $pp$ collisions at the LHC at a centre-of-mass energy of $5\,$TeV. The data sample corresponds to an integrated luminosity of $8.60\pm0.33\,$pb$^{-1}$ collected by the LHCb experiment. The production cross-sections of $D^0$, $D^+$, $D_s^+$, and $D^{*+}$ mesons are measured in bins of charm meson transverse momentum, $p_{\text{T}}$, and rapidity, $y$. They cover the rapidity range $2.0 < y < 4.5$ and transverse momentum ranges $0 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D^0$ and $D^+$ and $1 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D_s^+$ and $D^{*+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of $1 < p_{\text{T}} < 8\, \text{GeV}/c$ are determined to be \begin{equation*} \sigma(pp\rightarrow D^0 X) = 1190 \pm 3 \pm 64\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D^+ X) = 456 \pm 3 \pm 34\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D_s^+ X) = 195 \pm 4 \pm 19\,\mu\text{b} \end{equation*} \begin{equation*} \sigma(pp\rightarrow D^{*+} X)= 467 \pm 6 \pm 40\,\mu\text{b} \end{equation*} where the uncertainties are statistical and systematic, respectively.Production cross-sections of prompt charm mesons are measured using data from pp collisions at the LHC at a centre-of-mass energy of 5 TeV. The data sample corresponds to an integrated luminosity of 8.60 ± 0.33 pb$^{−1}$ collected by the LHCb experiment. The production cross-sections of D$^{0}$, D$^{+}$, D$_{s}^{+}$ , and D$^{∗+}$ mesons are measured in bins of charm meson transverse momentum, p$_{T}$, and rapidity, y. They cover the rapidity range 2.0 < y < 4.5 and transverse momentum ranges 0 < p$_{T}$ < 10 GeV/c for D$^{0}$ and D$^{+}$ and 1 < p$_{T}$ < 10 GeV/c for D$_{s}^{+}$ and D$^{∗+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of 1 < p$_{T}$ < 8 GeV/c are determined to be $\begin{array}{l}\sigma \left( pp\to {D}^0X\right)=1004\pm 3\pm 54\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}^{+}X\right)=402\pm 2\pm 30\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}_s^{+}X\right)=170\pm 4\pm 16\mu \mathrm{b},\\ {}\sigma \left( pp\to {D}^{\ast +}X\right)=421\pm 5\pm 36\mu \mathrm{b},\end{array}$ where the uncertainties are statistical and systematic, respectively.Production cross-sections of prompt charm mesons are measured using data from $pp$ collisions at the LHC at a centre-of-mass energy of $5\,$TeV. The data sample corresponds to an integrated luminosity of $8.60\pm0.33\,$pb$^{-1}$ collected by the LHCb experiment. The production cross-sections of $D^0$, $D^+$, $D_s^+$, and $D^{*+}$ mesons are measured in bins of charm meson transverse momentum, $p_{\text{T}}$, and rapidity, $y$. They cover the rapidity range $2.0<y<4.5$ and transverse momentum ranges $0 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D^0$ and $D^+$ and $1 < p_{\text{T}} < 10\, \text{GeV}/c$ for $D_s^+$ and $D^{*+}$ mesons. The inclusive cross-sections for the four mesons, including charge-conjugate states, within the range of $1 < p_{\text{T}} < 8\, \text{GeV}/c$ are determined to be \sigma(pp\rightarrow D^0 X) = 1004 \pm 3 \pm 54\,\mu\text{b} \sigma(pp\rightarrow D^+ X) = 402 \pm 2 \pm 30\,\mu\text{b} \sigma(pp\rightarrow D_s^+ X) = 170 \pm 4 \pm 16\,\mu\text{b} \sigma(pp\rightarrow D^{*+} X)= 421 \pm 5 \pm 36\,\mu\text{b} where the uncertainties are statistical and systematic, respectively