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Glioblastoma (GBM) is still an incurable tumor that is associated with high recurrence rate and poor survival despite the current treatment regimes. With the urgent need for novel therapeutic strategies, immunotherapies, especially chimeric antigen receptor (CAR)-expressing T cells, represent a promising approach for specific and effective targeting of GBM. However, CAR T cells can be associated with serious side effects. To overcome such limitation, we applied our switchable RevCAR system to target both the epidermal growth factor receptor (EGFR) and the disialoganglioside GD2, which are expressed in GBM. The RevCAR system is a modular platform that enables controllability, improves safety, specificity and flexibility. Briefly, it consists of RevCAR T cells having a peptide epitope as extracellular domain, and a bispecific target module (RevTM). The RevTM acts as a switch key that recognizes the RevCAR epitope and the tumor-associated antigen, and thereby activating the RevCAR T cells to kill the tumor cells. However, in the absence of the RevTM, the RevCAR T cells are switched off. In this study, we show that the novel EGFR/GD2-specific RevTMs can selectively activate RevCAR T cells to kill GBM cells. Moreover, we show that gated targeting of GBM is possible with our Dual-RevCAR T cells, which have their internal activation and co-stimulatory domains separated into two receptors. Therefore, a full activation of Dual-RevCAR T cells can only be achieved when both receptors recognize EGFR and GD2 simultaneously via RevTMs, leading to a significant killing of GBM cells both in vitro and in vivo.

We use a background quasar to detect the presence of circumgalactic gas around a z = 0.91 low-mass star-forming galaxy. Data from the new Multi Unit Spectroscopic Explorer (MUSE) on the Very Large Telescope show that the galaxy has a dust-corrected star formation rate (SFR) of 4.7 ± 2.0 M⊙ yr-1, with no companion down to 0.22 M⊙ yr-1 (5σ) within 240 h-1 kpc ("30"). Using a high-resolution spectrum of the background quasar, which is fortuitously aligned with the galaxy major axis (with an azimuth angle α of only 15°), we find, in the gas kinematics traced by low-ionization lines, distinct signatures consistent with those expected for a "cold-flow disk" extending at least 12 kpc (3 × R1/2). We estimate the mass accretion rate Ṁin to be at least two to three times larger than the SFR, using the geometric constraints from the IFU data and the H I column density of log NH I/cm-2 ≃ 20.4 obtained from a Hubble Space Telescope/COS near-UV spectrum. From a detailed analysis of the lowionization lines (e.g., Zn II, Cr II, Ti II, Mn II, Si II), the accreting material appears to be enriched to about 0.4 Z⊙ (albeit with large uncertainties: log Z/Z⊙ = -0.4 ± 0.4), which is comparable to the galaxy metallicity (12 + log O/H = 8.7 ± 0.2), implying a large recycling fraction from past outflows. Blueshifted Mg II and Fe II absorptions in the galaxy spectrum from the MUSE data reveal the presence of an outflow. The Mg II and Fe II absorption line ratios indicate emission infilling due to scattering processes, but the MUSE data do not show any signs of fluorescent Fe II∗ emission.

We present the results obtained with MUSE on the core of the lensing cluster A1689. Integral-field observations with MUSE provide a unique view of the central region, allowing us to conduct a complete census on both cluster galaxies and lensed background sources, identified based on their spectral features without preselection. We investigate the multiple-image configuration for all known sources in the field. Previous to our survey, 28 different lensed galaxies displaying 46 multiple images were known in the MUSE field of view, most of them based on photometric redshifts and lensing considerations. Among them, we spectroscopically confirm 12 images based on their emission-lines, corresponding to 7 different lensed galaxies between z = 0.95 and 5.0. In addition, 14 new galaxies have been spectroscopically identified in this area, with redshifts ranging between 0.8 and 6.2. All background sources within the MUSE field of view correspond to multiple-imaged systems lensed by A1689. 17 sources in total are found at z > 3 based on their Lyman-alpha emission, with Lyman-alpha luminosities ranging between 40.5 < log(Ly{\alpha}) < 42.5 after correction for magnification. This sample is particularly sensitive to the slope of the LF toward the faintest-end. The density of sources obtained in this survey is consistent with a steep value of {\alpha} < -1.5, although this result still needs further investigation. These results illustrate the efficiency of MUSE in the characterization of lensing clusters on one hand, and the study of faint and distant populations of galaxies on the other hand. In particular, our current survey of lensing clusters should provide a unique census of sources responsible for the reionization in a representative volume at z ~ 4-7., Comment: 12 pages, 11 figures

We use a background quasar to detect the presence of circum-galactic gas around a $z=0.91$ low-mass star forming galaxy. Data from the new Multi Unit Spectroscopic Explorer (MUSE) on the VLT show that the host galaxy has a dust-corrected star-formation rate (SFR) of 4.7$\pm$0.2 Msun/yr, with no companion down to 0.22 Msun/yr (5 $\sigma$) within 240 kpc (30"). Using a high-resolution spectrum (UVES) of the background quasar, which is fortuitously aligned with the galaxy major axis (with an azimuth angle $\alpha$ of only $15^\circ$), we find, in the gas kinematics traced by low-ionization lines, distinct signatures consistent with those expected for a "cold flow disk" extending at least 12 kpc ($3\times R_{1/2}$). We estimate the mass accretion rate $\dot M_{\rm in}$ to be at least two to three times larger than the SFR, using the geometric constraints from the IFU data and the HI column density of $\log N_{\rm HI} \simeq 20.4$ obtained from a {\it HST}/COS NUV spectrum. From a detailed analysis of the low-ionization lines (e.g. ZnII, CrII, TiII, MnII, SiII), the accreting material appears to be enriched to about 0.4 $Z_\odot$ (albeit with large uncertainties: $\log Z/Z_\odot=-0.4~\pm~0.4$), which is comparable to the galaxy metallicity ($12+\log \rm O/H=8.7\pm0.2$), implying a large recycling fraction from past outflows. Blue-shifted MgII and FeII absorptions in the galaxy spectrum from the MUSE data reveal the presence of an outflow. The MgII and FeII doublet ratios indicate emission infilling due to scattering processes, but the MUSE data do not show any signs of fluorescent FeII* emission., Comment: 17 pages, 11 figures, in press (ApJ), minor edits after the proofs. Data available at http://muse-vlt.eu/science/j1422/