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Development of antidrug antibodies (ADAs) is an undesirable potential outcome of administration of biotherapeutics and involves the innate and adaptive immune systems. ADAs can have detrimental clinical consequences: they can reduce biotherapeutic efficacy or produce adverse events. Because animal models are considered poor predictors of immunogenicity in humans, assays with human innate and adaptive immune cells are commonly used alternatives that can reveal cell-mediated unwanted immune responses. Multiple methods have been developed to assess the immune cell response following exposure to biotherapeutics and estimate the potential immunogenicity of biotherapeutics. This review highlights the role of innate and adaptive immune cells as the drivers of immunogenicity and summarizes the use of these cells in assays to predict clinical ADA.
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http://dx.doi.org/10.4155/bio-2021-0077 | DOI Listing |
AAPS J
September 2025
Gene Transfer and Immunogenicity Branch, Division of Gene Therapy 2, Office of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, WO52 RM3124, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993-0002, USA.
As the field of gene therapy advances and as the importance of sex as a biological variable in shaping viral immune responses is recognized, the impact of sex on adeno-associated virus (AAV) vectors mediated gene therapies remain largely unexplored. Here we review current understanding of the immune response against AAV gene therapy as well as the knowledge of sex differences observed in viral responses. We discuss sex differences in innate immune mechanisms such as Toll-like receptor recognition and complement activation, as well as the functional responses of key immune cells such as dendritic cells, macrophages, and T/B cells that are involved in AAV immunogenicity.
View Article and Find Full Text PDFCell Mol Immunol
September 2025
Pediatric Intensive Care Unit, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences); Department of Immunology, School of Basic Medical Sciences; Department of Clinical Laboratory, the Third Affiliated Hospital of Southern Medical University, Southern Medical University, Gua
Communication between group 3 innate lymphoid cells (ILC3) and other immune cells, as well as intestinal epithelial cells, is pivotal in regulating intestinal inflammation. This study, for the first time, underscores the importance of crosstalk between intestinal endothelial cells (ECs) and ILC3. Our single-cell transcriptome analysis combined with protein expression detection revealed that ECs significantly increased the population of interleukin (IL)-22 ILC3 through interactions mediated by endothelin-1 (ET-1) and its receptor endothelin A receptor (EDNRA).
View Article and Find Full Text PDFJ Immunother Cancer
September 2025
Harold C Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.
Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.
Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57 T and natural killer (NK) T cells, plasmablasts, proliferating and activated CXCR3 lymphocytes, CD8 effector and terminal effector memory T cells, along with reduced NK cells and elevated plasma ANA levels.
Ann N Y Acad Sci
September 2025
Department of Mammalogy, American Museum of Natural History, New York, New York, USA.
Our understanding of bat immunoglobulins (Igs) and their functions remains limited despite the importance of Ig activation in both innate and adaptive immune responses. Positive selection is known to act on other immune genes needed to mount adaptive immune responses, suggesting that selection may also act on bat Ig constant regions. To test whether bat Ig constant regions have evolved adaptations related to immunity, we reconstructed the evolutionary relationships of the constant region of bat IgM, IgA, and IgG genes and analyzed their sequences for signs of selection.
View Article and Find Full Text PDFBiomater Sci
September 2025
Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin, 300192, China.
Various cancer therapeutic strategies have been designed for targeting tumor-associated macrophages (TAMs), but TAM reprogramming-based monotherapy is often clinically hindered, likely due to the lack of a coordinated platform to initiate T cell-mediated immunity. Herein, we fabricated reactive oxygen species (ROS)-responsive human serum albumin (HSA)-based nanoparticles (PEG/IL12-IA NPs) consisting of indocyanine green (ICG), arginine (Arg), and interleukin 12 (IL12). Upon laser irradiation, the nanoparticles were found to be able to dissociate, thus facilitating the release of IL12.
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