It is well known that the serum of SLE patients contain anti-lymphocyte antibodies (ALA). In this paper we present a new rosette-forming assay for investigation of ALA. The method is based on the first step of antibody dependent cellular cytotoxicity (ADCC): the adherence of Fc-receptor bearing effector cells to the lymphocytes coated by antibodies. SLE serum samples were tested simultaneously by the new method (the rosette-test, RT) and the microcytotoxicity test (MCT) based on the complement mediated lysis. The results obtained by use of MCT and RT showed that the latter is suitable for investigation of ALA, indeed its diagnostic parameters are better than those of MCT. Moreover these results suggest that the two tests may differ in the antibody class detected. The new method is simple, time saving and demands no 51Cr-isotope as other ADCC tests do.
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CPT Pharmacometrics Syst Pharmacol
December 2024
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
In oncology drug development, measuring drug concentrations at the tumor site and at the targeted receptor remains an ongoing challenge. Positron emission tomography (PET)-imaging is a promising noninvasive method to quantify intratumor exposure of a radiolabeled drug (biodistribution data) and target saturation by treatment doses in vivo. Here, we present the development and application of a minimal physiologically-based pharmacokinetic (mPBPK) modeling approach to integrate biodistribution data in a quantitative platform to characterize and predict intratumor exposure and receptor occupancy (RO) of BI 754111, an IgG-based anti-lymphocyte-activation gene 3 (LAG-3) monoclonal antibody (mAb).
View Article and Find Full Text PDFInt J Mol Sci
September 2024
Department of Surgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
Predictive biomarkers for immune checkpoint inhibitors (ICIs) in solid tumors such as melanoma, hepatocellular carcinoma (HCC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), endometrial carcinoma, renal cell carcinoma (RCC), or urothelial carcinoma (UC) include programmed cell death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), defective deoxyribonucleic acid (DNA) mismatch repair (dMMR), microsatellite instability (MSI), and the tumor microenvironment (TME). Over the past decade, several types of ICIs, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, anti-programmed cell death 1 (PD-1) antibodies, anti-programmed cell death ligand 1 (PD-L1) antibodies, and anti-lymphocyte activation gene-3 (LAG-3) antibodies have been studied and approved by the Food and Drug Administration (FDA), with ongoing research on others. Recent studies highlight the critical role of the gut microbiome in influencing a positive therapeutic response to ICIs, emphasizing the importance of modeling factors that can maintain a healthy microbiome.
View Article and Find Full Text PDFTheranostics
September 2024
Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University Hospital Tuebingen, University of Tuebingen, Tuebingen, Germany.
Increasing evidence emphasizes the pivotal role of CD4 T cells in orchestrating cancer immunity. Noninvasive imaging of the temporal dynamics of CD4 T cells and their distribution patterns might provide novel insights into their effector and regulator cell functions during cancer immunotherapy (CIT). We conducted a comparative analysis of Zr-labeled anti-mouse (m) and anti-human (h) CD4-targeting minibodies (Mbs) for positron emission tomography (PET)/magnetic resonance imaging (MRI) of CD4 T cells in human xenografts, syngeneic tumor-bearing wild-type (WT), and human CD4 knock-in (hCD4-KI) mouse models.
View Article and Find Full Text PDFProtein Expr Purif
October 2024
Dongguan Key Laboratory of Molecular Immunology and Cell Therapy, The First Dongguan Affiliated Hospital, School of Medical Technology, Guangdong Medical University, Dongguan, Guangdong, 523808, China. Electronic address:
Objective: To screen and obtain specific anti-lymphocyte activation gene-3 (LAG3) nanobody sequences, purify and express recombinant anti-LAG3 nanobody, and verify its effect on promoting T cells to kill tumor cells.
Methods: Based on the camel derived natural nanobody phage display library constructed by the research group, the biotinylated LAG3 antigen was used as the target, and the anti-LAG3 nanobody sequences were screened by biotin-streptavidin liquid phase screening, phage-ELISA and sequencing. The sequence-conjμgated human IgG1 Fc fragment was obtained, the recombinant anti-LAG3 nanobody expression vector was constructed, the expression of the recombinant anti-LAG3 nanobody was induced by IPTG and purified, and the characteristics and functions of the recombinant anti-LAG3 nanobody were verified by SDS-PAGE, Western blot, cytotoxicity assay, etc.
Am J Physiol Lung Cell Mol Physiol
August 2024
Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California, United States.
Neutrophils are the first leukocytes to be recruited to sites of inflammation in response to chemotactic factors released by activated macrophages and pulmonary epithelial and endothelial cells in bacterial pneumonia, a common cause of acute respiratory distress syndrome (ARDS). Although neutrophilic inflammation facilitates the elimination of pathogens, neutrophils also may cause bystander tissue injury. Even though the presence of neutrophils in alveolar spaces is a key feature of acute lung injury and ARDS especially from pneumonia, their contribution to the pathogenesis of lung injury is uncertain.
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