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Deep learning-based design and experimental validation of a medicine-like human antibody library.
Brief Bioinform
November 2024
Biotherapeutics Molecule Discovery, Boehringer Ingelheim Pharmaceutical Inc., 900 Ridgebury Road, Ridgefield, CT 06877, United States.
Antibody generation requires the use of one or more time-consuming methods, namely animal immunization, and in vitro display technologies. However, the recent availability of large amounts of antibody sequence and structural data in the public domain along with the advent of generative deep learning algorithms raises the possibility of computationally generating novel antibody sequences with desirable developability attributes. Here, we describe a deep learning model for computationally generating libraries of highly human antibody variable regions whose intrinsic physicochemical properties resemble those of the variable regions of the marketed antibody-based biotherapeutics (medicine-likeness).
View Article and Find Full Text PDFSubtype-specific human endogenous retrovirus K102 envelope protein is a novel serum immunosuppressive biomarker of cancer.
Front Immunol
January 2025
Department of Hematology and Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Immune dysfunction is one of the hallmarks of cancer and plays critical roles in immunotherapy resistance, but there is no serum biomarker that can be used to evaluate immune-dysfunction status of cancer patients. Here, we identified subtype-specific human endogenous retrovirus K102 envelope (HERV-K102-Env) with immunosuppressive activity in circulating blood as a novel serum immunosuppressive biomarker of cancer. We first generated monoclonal antibodies against K102-Env with high sensitivity and specificity, and we developed an ELISA assay to detect serum K102-Env.
View Article and Find Full Text PDFEosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort study.
Front Immunol
January 2025
Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Introduction: Immune-related adverse events (irAEs) induced by immune checkpoint inhibitors are difficult to predict and can lead to severe events. Although it is important to develop strategies for the early detection of severe irAEs, there is a lack of evidence on irAEs associated with ipilimumab plus nivolumab therapy for metastatic renal cell carcinoma (RCC). Therefore, this study aimed to investigate the association between eosinophil and severe irAEs in patients receiving ipilimumab plus nivolumab therapy for RCC.
View Article and Find Full Text PDFNo correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy.
Res Pract Thromb Haemost
January 2025
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Background: Emicizumab, a bispecific antibody that mimics factor (F)VIII, has significantly improved hemophilia A management. Although emicizumab levels can be measured, tools for estimating the hemostatic efficacy of emicizumab are lacking. Thrombin generation (TG) assays can distinguish bleeding phenotypes in persons with hemophilia A on FVIII prophylaxis and may also be used during emicizumab therapy.
View Article and Find Full Text PDFSpatiotemporal regulation of alginate sub-structures at multiple scales revealed by monoclonal antibodies.
Cell Surf
June 2025
School of Natural and Environmental Sciences, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK.
Alginates are abundant linear polysaccharides produced by brown algae and some bacteria. They have multiple biological roles and important medical and commercial uses. Alginates are comprised of D-mannuronic acid (M) and L-guluronic acid (G) and the ratios and distribution patterns of M and G profoundly impact their physiological and rheological properties.
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