The programmed cell death protein 1 (PD-1, CD279) is an important therapeutic target in many oncological diseases. This checkpoint protein inhibits T lymphocytes from attacking other cells in the body and thus blocking it improves the clearance of tumor cells by the immune system. While there are already multiple FDA-approved anti-PD-1 antibodies, including nivolumab ( from Bristol-Myers Squibb) and pembrolizumab ( from Merck), there are ongoing efforts to discover new and improved checkpoint inhibitor therapeutics. In this study, we present multiple anti-PD-1 antibody fragments that were derived computationally using protein diffusion and evaluated through our scalable, pipeline. Here we present nine synthetic Fv structures that are suitable for further empirical testing of their anti-PD-1 activity due to desirable predicted binding performance.
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http://dx.doi.org/10.1177/15330338241275947 | DOI Listing |
Annu Rev Biomed Eng
January 2025
1Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA; email:
Biochemical signals in native tissue microenvironments instruct cell behavior during many biological processes ranging from developmental morphogenesis and tissue regeneration to tumor metastasis and disease progression. The detection and characterization of these signals using spatial and highly resolved quantitative methods have revealed their existence as matricellular proteins in the matrisome, some of which are bound to the extracellular matrix while others are freely diffusing. Including these biochemical signals in engineered biomaterials can impart enhanced functionality and native-like complexity, ultimately benefiting efforts to understand, model, and treat various diseases.
View Article and Find Full Text PDFBiochemistry
January 2025
BHF Centre of Research Excellence, School of Medicine and Life Sciences, King's College London, London SE1 9NH, United Kingdom.
Transmembrane glucose transport, facilitated by glucose transporters (GLUTs), is commonly understood through the simple mobile carrier model (SMCM), which suggests that the central binding site alternates exposure between the inside and outside of the cell, facilitating glucose exchange. An alternative "multisite model" posits that glucose transport is a stochastic diffusion process between ligand-operated gates within the transporter's central channel. This study aims to test these models by conducting atomistic molecular dynamics simulations of multiple glucose molecules docked along the central cleft of GLUT1 at temperatures both above and below the lipid bilayer melting point.
View Article and Find Full Text PDFDiffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous metastatic lymphoma that can be treated by targeting angiogenesis. Apolipoprotein C1 (APOC1) plays a significant role in the proliferation and metastasis of various malignant tumors; however, its role in DLBCL-particularly its effects on angiogenesis-remains largely unexplored. This study investigates the correlation between APOC1 expression and patient prognosis in DLBCL.
View Article and Find Full Text PDFBrain
January 2025
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Although the pathophysiology of migraine involves a complex ensemble of peripheral and central nervous system changes that remain incompletely understood, the activation and sensitization of the trigeminovascular system is believed to play a major role. However, non-invasive, in vivo neuroimaging studies investigating the underlying neural mechanisms of trigeminal system abnormalities in human migraine patients are limited. Here, we studied 60 patients with migraine (55 females, mean age ± SD: 36.
View Article and Find Full Text PDFGenes Chromosomes Cancer
January 2025
Department of Pathology, NYU Grossman School of Medicine, New York, New York, USA.
Gene fusions involving JAZF1 are a recurrent event in low grade endometrial stromal sarcoma, and have been more recently described in few instances of endometrial stromal sarcoma-like tumors in the genitourinary tract of men. In this article, we describe a previously unreported spindle cell sarcoma harboring an in-frame JAZF1::NUDT5 gene fusion, arising in the chest wall of a 51-year-old man. The tumor had unique morphologic features resembling both endometrial stromal sarcoma and endometrial stromal sarcoma-like tumors, consisting of a mixture of cytologically bland and pleomorphic spindle cells with brisk mitotic activity, within an alternating myxoid and fibrous stroma.
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