The CD47/signal regulatory protein α (Cd47/SIRPα)interaction provides a macrophage immune checkpoint pathway that plays a critical role in cancer immune evasion across multiple cancers. Here, we report the engineering of a humanized anti-SIRPα monoclonal antibody (1H9) for antibody target cancer therapy. 1H9 has broad activity across a wide range of SIRPα variants. Binding of 1H9 to SIRPα blocks its interaction with CD47, thereby promoting macrophage-mediated phagocytosis of cancer cells. Preclinical studies in vitro and in vivo demonstrate that 1H9 synergizes with other therapeutic antibodies to promote phagocytosis of tumor cells and inhibit tumor growth in both syngeneic and xenograft tumor models, leading to survival benefit. Thus, 1H9 can potentially act as a universal agent to enhance therapeutic efficacy when used in combination with most tumor-targeting antibodies. We report a comparison of anti-SIRPα and anti-CD47 antibodies in CD47/SIRPα double-humanized mice and found that 1H9 exhibits a substantially reduced antigen sink effect due to the limited tissue distribution of SIRPα expression. Toxicokinetic studies in nonhuman primates show that 1H9 is well tolerated, with no treatment-related adverse effects noted. These data highlight the clinical potential of 1H9 as a pan-therapeutic with the desired properties when used in combination with tumor-targeting antibodies.
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http://dx.doi.org/10.1172/jci.insight.134728 | DOI Listing |
Nano Lett
January 2025
Department of Mechanical Engineering, University of Alberta, 9211-116 Street NW, Edmonton, Alberta T6G 1H9, Canada.
Uncontrolled lithium (Li) dendrite formation presents major safety risks and challenges in the Li host design. A novel approach is introduced, using a valence gradient in iron nanoparticles (Fe, Fe, Fe) to stabilize the anodes. An Fe component, with fast Li diffusion, ensures a steady supply of Li to Fe and Fe components, which have slower Li diffusion.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
School of Chemical Engineering and Technology, China University of Mining and Technology, Xuzhou 221116, China.
Bubbles present in saline water typically exhibit a prolonged lifetime, making them attractive for various engineering processes. Herein, we unveil a transition from delayed bubble coalescence to rapid bursting within about one millisecond in salty solutions. The key aspect in understanding this transition lies in the combined influences of surface deformation and ion surface excess instead of characterizing the ions alone.
View Article and Find Full Text PDFEnviron Pollut
January 2025
School of Civil & Environmental Engineering and Geography Science, Ningbo University, Ningbo 315211, China; Institute of Hydraulic and Ocean Engineering, Ningbo University, Ningbo 315211, China. Electronic address:
Escherichia coli (E. coli) O157:H7 is a highly pathogenic zoonotic bacterium, with water serving as a key medium for its environmental transmission. However, the survival characteristics of E.
View Article and Find Full Text PDFRSC Adv
January 2025
Department of Chemical and Materials Engineering, University of Alberta Edmonton AB T6G 1H9 Canada
Non-destructive color sensors are widely applied for rapid analysis of various biological and healthcare point-of-care applications. However, existing red, green, blue (RGB)-based color sensor systems, relying on the conversion to human-perceptible color spaces like hue, saturation, lightness (HSL), hue, saturation, value (HSV), as well as cyan, magenta, yellow, key (CMYK) and the CIE L*a*b* (CIELAB) exhibit limitations compared to spectroscopic methods. The integration of machine learning (ML) techniques presents an opportunity to enhance data analysis and interpretation, enabling insights discovery, prediction, process automation, and decision-making.
View Article and Find Full Text PDFWaste Manag
January 2025
Department of Mechanical Engineering, University of Alberta, 10-203 Donadeo Innovation Centre for Engineering, Edmonton, Alberta T6G 1H9, Canada. Electronic address:
Bitumen-derived petcoke contains significant quantities of vanadium, recoverable from the fly ash formed during combustion. Despite efforts to process vanadium recovery from petcoke, detailed cost information, critical for stakeholders and decision-makers, remains absent in the public domain. To address this gap, we developed data-intensive techno-economic models specifically for vanadium recovery from petcoke fly ash.
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