CD46

An antibody-drug conjugate (ADC) targeting CD46 conjugated to monomethyl auristatin has a potent anti-myeloma effect in cell lines in vitro and in vivo, and patient samples treated ex vivo. Here, we tested if CD46-ADC may have the potential to target MM-initiating cells (MM-ICs). CD46 expression was measured on primary MM cells with a stem-like phenotype. A patient-derived xenograft (PDX) model was implemented utilizing implanted fetal bone fragments to provide a humanized microenvironment. Engraftment was monitored via serum human light chain ELISA, and at sacrifice via bone marrow and bone fragment flow cytometry...

INTRODUCTION: Stratification of Alzheimer's disease (AD) patients into risk subgroups using Polygenic Risk Scores (PRS) presents novel opportunities for the development of clinical trials and disease-modifying therapies. However, the heterogeneous nature of AD continues to pose significant challenges for the clinical broadscale use of PRS. PRS remains unfit in demonstrating sufficient accuracy in risk prediction, particularly for individuals with mild cognitive impairment (MCI), and in allowing feasible interpretation of specific genes or SNPs contributing to disease risk...

CD46 is a complementary regulatory protein ubiquitously expressed in human cells, controlling complement system activation. CD46 has further been identified to have several other functions including regulatory T cell induction and intestinal epithelial (IEC) barrier regulation. Activation of CD46 in the IEC can impact intestinal barrier permeability and immune system functioning. CD46 has only been identified in the spermatozoa and retina of mice. In other murine cells, the homologue CRRY is identified to function as the complementary regulator...

PURPOSE OF REVIEW: The first successful pig to human cardiac xenotransplantation in January 2022 represented a major step forward in the fields of heart failure, immunology, and applied genetic engineering, using a 10-gene edited (GE) pig. This review summarizes the evolution of preclinical modelling data which informed the use of each of the 10 genes modified in the 10-GE pig: GGTA1, Β4GalNT2, CMAH, CD46, CD55, TBM, EPCR, CD47, HO-1, and growth hormone receptor. RECENT FINDINGS: The translation of the 10-GE pig from preclinical modelling to clinical compassionate xenotransplant use was the culmination of decades of research combating rejection, coagulopathy, inflammation, and excessive xenograft growth...

Among human species B adenovirus, HAdV-11, has the particular feature of exploiting two primary receptors, desmoglein 2 (DSG2) and CD46, to mediate cell attachment. This serotype represents a particularly promising class of oncolytic viral vaccines. For instance, Enadenotucirev, a species B HAdV-11/HAdV-3 chimeric adenoviral vector, demonstrated preclinical tumor-selective cytotoxicity. Understanding the mechanism of HAdV-11 entry is a major challenge for the development of powerful vectors. Interactions between HAdV-11 and CD46 are well-characterized and clearly depend on the fiber protein, but the mechanism whereby HAdV-11 engages DSG2 has been still unresolved...

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (Cas9) system is the most efficient and widely used technology for genome editing in all sorts of organisms, including livestock animals. Here, we examined the feasibility of CRISPR/Cas9-derived genome editing (GE) in vitrified porcine zygotes, where the flexible planning of experiments in time and space is expected. OCT4 and CD46 genes were targeted, and the Cas9/sgRNA ribonucleoprotein complexes (RNP) were electroporated into zygotes at 2 h after warming...

BACKGROUND: Homozygous CD59-deficient patients manifest with recurrent peripheral neuropathy resembling Guillain-Barré syndrome (GBS), hemolytic anemia and recurrent strokes. Variable mutations in CD59 leading to loss of function have been described and, overall, 17/18 of patients with any mutation presented with recurrent GBS. Here we determine the localization and possible role of membrane-bound complement regulators, including CD59, in the peripheral nervous systems (PNS) of mice and humans...

CD46 is a membrane-bound complement regulatory protein (mCRP) possessing a regulatory role with the complement system. CD46 protects the host cells from damage by complement. Expression of CD46 is also highly maintained in many cancers, including bladder cancers, and thus functions as a receptor for many cancer therapeutic viruses. In this study we report a unique role of CD46 as a progression factor of cancer cells in bladder cancers. Resulting data from a DNA microarray using CD46-altered HT1376 bladder cancers demonstrated a pool of target genes, including complement C3 α chain (C3α), matrix Gla protein (MGP), AFAP-AS1, follicular dendritic cell secreted protein (FDCSP), MAM domain containing 2 (MAMDC2), gamma-aminobutyric acid A receptor pi (GABRP), transforming growth factor, beta-induced (TGFBI), a family of cytochrome P450 (CYP24A1), sialic acid binding Ig-like lectin 6 (SIGLEC6), metallothionein 1E (MT1E), and several members of cytokeratins...

Cardiac xenotransplantation is the potential treatment for end-stage heart failure, but the allogenic organ supply needs to catch up to clinical demand. Therefore, genetically-modified porcine heart xenotransplantation could be a potential alternative. So far, pig-to-monkey heart xenografts have been studied using multi-transgenic pigs, indicating various survival periods. However, functional mechanisms based on survival period-related gene expression are unclear. This study aimed to identify the differential mechanisms between pig-to-monkey post-xenotransplantation long- and short-term survivals...

OBJECTIVE: Non-cirrhotic intrahepatic portal hypertension (NCIPH), a portal microangiopathy affecting small portal vein radicles, is a disease of Indian sub-continent. NCIPH appears to be a complex disease with interactions between inherited and acquired factors, though the exact pathophysiological mechanism is unknown. We aimed at investigating the genetic variants that might contribute to susceptibility to NCIPH. METHODS: In this case-control study, we analyzed genes associated with microangiopathy-VWF-ADAMTS13 (von Willebrand factor and its cleavase enzyme - a disintegrin and matrix metalloprotease with thrombospondin type-1 motifs member 13) and alternative complement system vitamin B12 metabolism and with familial NCIPH...

Classical swine fever virus (CSFV), which is a positive-sense, single-stranded RNA virus with an envelope, is a member of the Pestivirus genus in the Flaviviridae family. CSFV causes a severe and highly contagious disease in pigs and is prevalent worldwide, threatening the pig farming industry. The detailed mechanisms of the CSFV life cycle have been reported, but are still limited. Some receptors and attachment factors of CSFV, including heparan sulfate (HS), laminin receptor (LamR), complement regulatory protein (CD46), MER tyrosine kinase (MERTK), disintegrin, and metalloproteinase domain-containing protein 17 (ADAM17), were identified...

Xenotransplantation is a promising approach to reduce organ shortage, while genetic modification of donor pigs has significantly decreased the immunogenic burden of xenotransplants, organ rejection is still a hurdle. Genetically modified pig organs are used in xenotransplantation research, and the first clinical pig-to-human heart transplantation was performed in 2022. However, the impact of genetic modification has not been investigated on a cellular level yet. Endothelial cells (EC) and their sugar-rich surface known as the glycocalyx are the first barrier encountering the recipient's immune system, making them a target for rejection...

CD46, as a cofactor of complement I factor, not only regulates the complement system but also functions as a pathogen receptor and is involved in controlling early pathogen infection through autophagy. In this study, a new CD46 gene (ToCD46) was identified from golden pompano (Trachinotus ovatus), which showed higher sequence homology with other teleosts CD46. Homology comparison showed that ToCD46 had higher sequence homology (46.95-52.85%) with other teleosts CD46 and lower homology with mammal. Tissue expression profile analysis showed that ToCD46 was generally expressed in all tissues with the highest expression level in liver, followed by head kidney, and showed different patterns of up-regulation in immune-related tissues after stimulation by Streptococcus agalactiae and Vibrio alginolyticus...

Worldwide, cirrhosis is a common cause of death, manifesting itself as fibrosis of the liver tissue. When the liver is damaged, the liver produces fibrotic, proliferative myofibroblasts, which are formed by the differentiation of activated hepatic stellate cells. There are no effective antifibrotic treatment options. To deeply explore the activation process of hepatic stellate cells (HSCs) and to discover better therapeutic target genes, single-cell RNA sequencing data on 13 non-cirrhotic liver tissue samples and 10 cirrhotic liver tissue samples were analyzed...

Human cytomegalovirus (HCMV) primary infections are typically asymptomatic in healthy individuals yet can cause increased morbidity and mortality in organ transplant recipients, AIDS patients, neonates, and the elderly. The successful, widespread dissemination of this virus among the population can be attributed in part to its wide cellular tropism and ability to establish life-long latency. HCMV infection is a multi-step process that requires numerous cellular and viral factors. The viral envelope consists of envelope protein complexes that interact with cellular factors; such interactions dictate virus recognition and attachment to different cell types, followed by fusion either at the cell membrane or within an endocytic vesicle...

BACKGROUND: Allograft dysfunction (AGD) is a common complication following solid organ transplantation (SOT). This study leverages the potential of urinary extracellular vesicles (UEVs) for the non-invasive detection of AGD. AIM: We aimed to assess the diagnostic value of T-cell and B-cell markers characteristic of T-cell-mediated and antibody-mediated rejection in UEV-mRNA using renal transplantation as a model. MATERIALS AND METHODS: UEVs were isolated from 123 participants, spanning healthy controls, functional transplant recipients, and biopsy-proven AGD patients...

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder that can lead to heart failure and sudden cardiac death, characterized at the histological level by focal areas of myocyte disarray, hypertrophy and fibrosis, and only a few disease-targeted therapies exist. To identify the focal and spatially restricted alterations in the transcriptional pathways and reveal novel therapeutic targets, we performed a spatial transcriptomic analysis of the areas of focal myocyte disarray compared to areas of normal tissue using a commercially available platform (GeoMx, nanoString)...

AIM: Ovarian cancer is a serious malignancy with high prevalence and mortality. METHODS: We isolated and characterized an ovarian high-grade serous cancer cell line (M4) from a tumor of a Vietnamese patient with ovarian carcinoma. RESULTS: The M4 cancer cell line showed good proliferation and stability in culture. Morphologically, the M4 cells showed similar characteristics to tumor cells such as a polyhedral shape, large irregular nuclei, high nuclear/cytoplasmic ratio, high nuclear density and expressing cancer markers like CA125, p53 and Ki67 markers...

Peritoneal mesenchymal stromal cells (pMSCs) are isolated from peritoneal dialysis (PD) effluent, and treatment with the pMSCs reduces peritoneal membrane injury in rat model of PD. This study was designed to verify the identity of the pMSCs. pMSCs were grown in plastic dishes for 4-7 passages, and their cell surface phenotype was examined by staining with a panel of 242 antibodies. The positive stain of each target protein was determined by an increase in fluorescence intensity as compared with isotype controls in flow cytometrical analysis...

CD46 can facilitate the production of IgE. Activation of CD46 may contribute to the pathogenesis of allergic diseases. The aim of this study is to elucidate the association between CD46 expression in B cells and the pathogenesis of airway allergy. In this study, peripheral B cells were collected from a group of patients suffering from allergic rhinitis (AR). An AR mouse model was established to test the role of CD46 in the development of airway allergy. The results showed elevated amounts of IGE in peripheral CD46+ B cells of AR patients...