Treatment of nonhuman primates and mice with a humanized antigen-binding fragment (Fab) antibody (UCBFab) inhibiting transforming growth factor β via daily inhalation for up to 13 weeks resulted in low systemic exposure but high local exposure in the lung. Target engagement was demonstrated by reduced levels of signal transducers, phosphoSMAD and plasminogen activator inhibitor-1 in the bronchoalveolar lavage fluid (BALF). Treatment was associated with a high frequency and titer of antidrug antibodies, indicating high local immunogenicity, and local pathology within the lung and draining lymph nodes. Microscopic changes were characterized by perivascular (PV) and peribronchiolar (PB) mononuclear inflammatory cell (MIC) infiltrates that were principally lymphocytic in nature and mixed inflammatory cell infiltrates and/or inflammation within the alveoli. Immunohistochemical investigation revealed a predominantly CD68-positive macrophage and CD3- and CD8>CD4-positive T-cell response in the alveoli, whereas within the airways, there was a variable mixture of CD3-positive T cells, CD20-positive B cells, and CD68-positive macrophages. Increased cellularity of the draining lymph nodes was also noted, indicating the presence of an immune response to the inhaled test article. Morphologic changes did not progress over time, and all changes partially recovered. Increased leukocytes (principally macrophages) in BALF cytology correlated with the changes seen by histopathology.
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Biosens Bioelectron
December 2024
National Research Council (CNR), Institute of Applied Sciences and Intelligent Systems, I-80131, Naples, Italy. Electronic address:
Spectrochemical analysis of trace elements in complex matrices is crucial across various fields of science, industry, and technology. However, this analysis is often hindered by background interference and the challenge of detecting ultralow analyte concentrations. Surface Enhanced Infrared Absorption (SEIRA) spectroscopy is emerging as a viable technique to address these challenges as it can successfully reveal soluble and unmodified analytes in a label-free manner through their interactions with a bioreceptor following site-specific labeling with small infrared-active probes.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Immunology and Theranostics, City of Hope, Duarte, CA, United States.
Introduction: Although CAR-T cell therapy has limited efficacy against solid tumors, it has been hypothesized that prior treatment with Image-Guided Radiation Therapy (IGRT) would increase CAR-T cell tumor infiltration, leading to improved antigen specific expansion of CAR-T cells.
Methods: To test this hypothesis in a metastatic triple negative breast cancer (TNBC) model, we engineered two anti-CEA single-chain Fab (scFab) CAR-T cells with signaling domains from CD28zeta and 4-1BBzeta, and tested them and .
Results: The anti-CEA scFab CAR-T cells generated from three different human donors demonstrated robust expression, expansion, and lysis of only CEA-positive TNBC cells, with the CD28z-CAR-T cells showing the highest cytotoxicity.
ACS Nano
January 2025
Institute of Biomedical Engineering, University of Toronto, Toronto M5S 2E3, Canada.
Immune complexes (ICs), formed via antibody (Ab)-antigen (Ag) binding, trigger diverse immune responses, which are critical for natural immunity and have uses for vaccines and immunotherapies. While IC-elicited immune responses depend on its structure, existing methods for IC synthesis produce heterogeneous assemblies, which limits control over their cellular interactions and pharmacokinetics. In this study, we demonstrate the use of DNA origami to create synthetic ICs with defined shape, size, and solubility by displaying Ags in prescribed spatial patterns.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Obstetrics and Gynecology Department, Tehran University of Medical Sciences, Tehran, Iran.
Breast cancer is the most frequent non-dermatologic malignancy in women. Breast cancer is characterized by the expression of the human epidermal growth factor receptor type 2 (HER2), and the presence or lack of estrogen receptor (ER) and progesterone receptor (PR) expression. HER2 overexpression is reported in about 20 to 25% of breast cancer patients, which is usually linked to cancer progression, metastases, and poor survival.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Chemistry, New York University, New York, NY, USA.
Advancements in cryo-EM have stimulated a revolution in structural biology. Yet, for membrane proteins near the cryo-EM size threshold of approximately 40 kDa, including transporters and G-protein coupled receptors, the absence of distinguishable structural features makes image alignment and structure determination a significant challenge. Furthermore, resolving more than one protein conformation within a sample, a major advantage of cryo-EM, represents an even greater degree of difficulty.
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