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Manufacturing autologous chimeric antigen receptor (CAR) T cell therapeutics is complex, and many patients experience treatment delays or cannot be treated at all. Although current allogeneic CAR products have the potential to overcome manufacturing bottlenecks, they are subject to immune rejection and failure to persist in the host, and thus do not provide the same level of efficacy as their autologous counterparts. Here, we aimed to develop universal allogeneic CAR T cells that evade the immune system and produce a durable response. We generated human hypoimmune (HIP) T cells with disrupted B2M, CIITA , and TRAC genes using CRISPR-Cas9 editing. In addition, CD47 and anti-CD19 CAR were expressed using lentiviral transduction. These allogeneic HIP CD19 CAR T cells were compared to allogeneic CD19 CAR T cells that only expressed the anti-CD19 CAR (allo CAR T). In vitro assays for cancer killing and exhaustion revealed no differences between allo CAR T and HIP CAR T cells, confirming that the HIP edits did not negatively affect T cell performance. Clearance of CD19 + tumors by HIP CAR T cells in immunodeficient NSG mice was comparable to that of allo CAR T cells. In fully immunocompetent humanized mice, HIP CAR T cells significantly outperformed allo CAR T cells, showed improved persistence and expansion, and provided lasting cancer clearance. Furthermore, CD47-targeting safety strategies reliably and specifically eliminated HIP CAR T cells. These findings suggest that universal allogeneic HIP CAR T cell-based therapeutics might overcome the limitations associated with poor persistence of allogeneic CAR T cells and exert durable anti-tumor responses. The development of allogeneic chimaeric antigen receptor (CAR) T cells could overcome manufacturing bottlenecks for immunotherapy. However, immune rejection reduces the persistence and efficacy of these cells. Here, the authors generate allogeneic anti-CD19 CAR T cells that can evade the immune system and provide durable anti-tumour responses.

The St. Lawrence is a vast and complex socio-ecological system providing a wealth of services sustaining numerous economic sectors. These ecosystems are subject to significant human pressures that overlap and potentially interact with climate driven environmental changes. Our objective in this paper is to systematically characterize the distribution and intensity of drivers in the St. Lawrence System. To do so, we launch eDrivers, an open knowledge platform gathering experts committed to structuring, standardizing and sharing knowledge on drivers in support of science and management. We gathered data on 22 coastal, climate, fisheries and marine traffic drivers through collaborations, existing environmental initiatives and open data portals. We show that few areas of the St. Lawrence are free of cumulative exposure. The Estuary, the Anticosti Gyre and coastal areas are particularly exposed, especially in the vicinity of urban centers. We identified 6 areas of distinct cumulative exposure regime that show that certain drivers typically co-occur in different regions of the St. Lawrence and that coastal areas are exposed to all driver types. Of particular concern are two threat complexes capturing most exposure hotspots that show the convergence of contrasting exposure regimes at the head of the Laurentian Channel. eDrivers was built on a series of guiding principles upholding existing data management and open science standards. We therefore expect it to evolve through time to address knowledge gaps and refine current driver layers. Ultimately, we believe that eDrivers represents a much needed solution that could radically influence broad scale research and management practices by increasing knowledge accessibility and interoperability.

We present an overview of the JWST GLIMPSE program, highlighting its survey design, primary science goals, gravitational lensing models, and first results. GLIMPSE provides ultra-deep JWST/NIRCam imaging across seven broadband filters (F090W, F115W, F200W, F277W, F356W, F444W) and two medium-band filters (F410M, F480M), with exposure times ranging from 20 to 40 hours per filter. This yields a 5\\(\\sigma\\) limiting magnitude of 30.9 AB (measured in a 0.2 arcsec diameter aperture). The field is supported by extensive ancillary data, including deep HST imaging from the Hubble Frontier Fields program, VLT/MUSE spectroscopy, and deep JWST/NIRSpec medium-resolution multi-object spectroscopy. Exploiting the strong gravitational lensing of the galaxy cluster Abell S1063, GLIMPSE probes intrinsic depths beyond 33 AB magnitudes and covers an effective source-plane area of approximately 4.4 arcmin\\(^2\\) at \\(z \\sim 6\\). The program's central aim is to constrain the abundance of the faintest galaxies from \\(z \\sim 6\\) up to the highest redshifts, providing crucial benchmarks for galaxy formation models, which have so far been tested primarily on relatively bright systems. We present an initial sample of \\(\\sim 540\\) galaxy candidates identified at \\(6 < z < 16\\), with intrinsic UV magnitudes spanning \\(M_{\\mathrm UV}\\) = \\(-\\)20 to \\(-\\)12. This enables unprecedented constraints on the extreme faint end of the UV luminosity function at these epochs. In addition, GLIMPSE opens new windows for spatially resolved studies of star clusters in early galaxies and the detection and characterization of faint high-\\(z\\) active galactic nuclei. This paper accompanies the first public data release, which includes reduced JWST and HST mosaics, photometric catalogs, and gravitational lensing models.