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Anti-Topoisomerase I Antibody

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101. Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity (PubMed)

Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity Targeted therapeutics that can differentiate between normal and malignant tumor cells represent the ideal standard for the development of a successful anti-cancer strategy. The Sialyl-Thomsen-nouveau antigen (STn or Sialyl-Tn, also known as CD175s) is rarely seen in normal adult tissues, but it is abundantly expressed in many types of human epithelial cancers. We have (...) identified novel antibodies that specifically target with high affinity the STn glycan independent of its carrier protein, affording the potential to recognize a wider array of cancer-specific sialylated proteins. A panel of murine monoclonal anti-STn therapeutic antibodies were generated and their binding specificity and efficacy were characterized in vitro and in in vivo murine cancer models. A subset of these antibodies were conjugated to monomethyl auristatin E (MMAE) to generate antibody-drug

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2017 mAbs

102. Anti-centromere antibody exhibits specific distribution levels among anti-nuclear antibodies and may characterize a distinct subset in rheumatoid arthritis (PubMed)

Anti-centromere antibody exhibits specific distribution levels among anti-nuclear antibodies and may characterize a distinct subset in rheumatoid arthritis Anti-centromere antibody (ACA) is one of the classical anti-nuclear antibody (ANA) staining patterns. However, characteristics of ACA in comparison with the other ANA patterns and clinical features of ACA-positive subjects have not been elucidated. Here, we examined all ANA patterns by indirect immunofluorescence for 859 rheumatoid arthritis

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2017 Scientific reports

103. Immunoglobulin-like Domain of <i>Hs</i>FcμR as a Capture Molecule for Detection of Crimean-Congo Hemorrhagic Fever Virus- and Zika Virus-Specific IgM Antibodies. (PubMed)

Immunoglobulin-like Domain of <i>Hsi>FcμR as a Capture Molecule for Detection of Crimean-Congo Hemorrhagic Fever Virus- and Zika Virus-Specific IgM Antibodies. The cellular surface molecule HsTOSO/FAIM3/HsFcμR has been identified as an IgM-specific Fc receptor expressed on lymphocytes. Here, we show that its extracellular immunoglobulin-like domain (HsFcμR-Igl) specifically binds to IgM/antigen immune complexes (ICs) and exploit this property for the development of novel detection systems (...) for IgM antibodies directed against Crimean-Congo hemorrhagic fever virus (CCHFV) and Zika virus (ZIKV).His-tagged HsFcμR-Igl was expressed in Escherichia coli and purified by affinity chromatography, oxidative refolding, and size-exclusion chromatography. Specific binding of HsFcμR-Igl to IgM/antigen ICs was confirmed, and 2 prototypic ELISAs for the detection of anti-CCHFV and anti-ZIKV IgM antibodies were developed. Thereby, patient sera and virus-specific recombinant antigens directly labeled

2019 Clinical Chemistry

104. HLA-Class I Sensitized Renal Transplant Patients have Antibody Binding to SLA-Class I Epitopes. (PubMed)

HLA-Class I Sensitized Renal Transplant Patients have Antibody Binding to SLA-Class I Epitopes. Highly sensitized patients are difficult to match with suitable renal allograft donors and may benefit from xenotransplant trials. We evaluate antibody binding from sensitized patients to pig cells and engineered single allele cells to identify anti-HLA antibody cross-species reactivity with swine leukocyte antigen (SLA). These novel testing strategies assess HLA/SLA epitopes and antibody binding (...) cells was minimized by CRISPR/Cas9 elimination of endogenous Class I and Class II HLA, b-cell receptor, and Fc-receptor genes. Native HLA, SLA, and mutants of these proteins after mutating 144K to Q were assessed for antibody binding.Those with predominately anti-HLA-B&C antibodies, including Bw6 and Bw4 sensitization, frequently have low pig reactivity. Conversely, antibodies eluted from porcine cells are more commonly anti-HLA-A. Single HLA/SLA antigen expressing engineered cells show variable

2019 Transplantation

105. Bayesian Evaluation of Three Serological Tests for Detecting Antibodies against <i>Brucella</i> spp. among Humans in the Northwestern Part of Ecuador. (PubMed)

Bayesian Evaluation of Three Serological Tests for Detecting Antibodies against <i>Brucellai> spp. among Humans in the Northwestern Part of Ecuador. Brucellosis is an important but neglected zoonosis that causes serious economic losses both in livestock and human populations. The aim of the present study was to estimate the true prevalence of brucellosis together with diagnostic sensitivity and specificity of three serological tests in humans of the northwestern part of Ecuador using

2019 American Journal of Tropical Medicine & Hygiene

106. Safety and Differential Antibody and T-Cell Responses to <i>Plasmodium falciparum</i> Sporozoite Vaccine by Age in Tanzanian Adults, Adolescents, Children, and Infants. (PubMed)

Safety and Differential Antibody and T-Cell Responses to <i>Plasmodium falciparumi> Sporozoite Vaccine by Age in Tanzanian Adults, Adolescents, Children, and Infants. In 2016, there were more cases and deaths caused by malaria globally than in 2015. An effective vaccine would be an ideal additional tool for reducing malaria's impact. Sanaria® PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum (Pf) sporozoites (SPZ) has been well tolerated (...) dosage regimens. Because all age groups received three doses of 9.0 × 105 PfSPZ of PfSPZ Vaccine, immune responses were compared at this dosage. Median antibody responses against Pf circumsporozoite protein and PfSPZ were highest in infants and lowest in adults. T-cell responses were highest in 6-10-year olds after one dose and 1-5-year olds after three doses; infants had no significant positive T-cell responses. The safety data were used to support initiation of trials in > 300 infants in Kenya

2019 American Journal of Tropical Medicine & Hygiene

107. Development of an Antigen Detection ELISA for Bancroftian Filariasis Using <i>Bm</i>SXP-Specific Recombinant Monoclonal Antibody. (PubMed)

Development of an Antigen Detection ELISA for Bancroftian Filariasis Using <i>Bmi>SXP-Specific Recombinant Monoclonal Antibody. Lymphatic filariasis is a mosquito-borne parasitic disease responsible for morbidity and disability that affects 1.2 billion people worldwide, mainly the poor communities. Currently, filarial antigen testing is the method of choice for the detection of bancroftian filariasis, and to date, there are two commonly used tests. In the present study, a recently reported (...) recombinant monoclonal antibody (5B) specific to BmSXP filarial antigen was used in developing an ELISA for the detection of circulating filarial antigen in sera of patients with bancroftian filariasis. The performance of the ELISA was evaluated using 124 serum samples. The ELISA was positive with all sera from microfilaremic bancroftian filariasis patients (n = 34). It also showed 100% diagnostic specificity when tested with sera from 50 healthy individuals and 40 patients with other parasitic diseases

2019 American Journal of Tropical Medicine & Hygiene

108. Efficacy of a multimechanistic monoclonal antibody combination against <i>Staphylococcus aureus</i> surgical site infections in mice. (PubMed)

Efficacy of a multimechanistic monoclonal antibody combination against <i>Staphylococcus aureusi> surgical site infections in mice. Surgical site infections (SSI) are commonly caused by Staphylococcus aureus Here, we report that a combination of three monoclonal antibodies (MEDI6389) that neutralize S. aureus α-toxin, clumping factor A and four leukocidins (LukSF, LukED, HlgAB and HlgCB) plus vancomycin had enhanced efficacy than control antibody plus vancomycin in two mouse models of S

2019 Antimicrobial Agents and Chemotherapy

109. Penetration of a Monoclonal Antibody Combination (ASN100) Targeting <i>S. aureus</i> Cytotoxins in Lung Epithelial Lining Fluid: A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study in Healthy Volunteers. (PubMed)

Penetration of a Monoclonal Antibody Combination (ASN100) Targeting <i>S. aureusi> Cytotoxins in Lung Epithelial Lining Fluid: A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study in Healthy Volunteers. ASN100 is a novel antibody combination of two fully human IgG1 kappa monoclonal antibodies, ASN-1 and ASN-2 which neutralize six Staphylococcus aureus cytotoxins, alpha-hemolysin (Hla) and five bi-component leukocidins. We assessed the safety, tolerability, and serum (...) to the Investigational Product. ASN100 exhibited linear serum PK with a half-life of approximately three weeks and showed detectable penetration into the ELF. No treatment-emergent anti-drug antibody responses were detected. The toxin neutralizing potency of ASN100 in human serum was confirmed up to 58 days post-dosing.The favorable safety profile, ELF penetration, and maintained functional activity in serum supported the further clinical development of ASN100.Copyright © 2019 Magyarics et al.

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2019 Antimicrobial Agents and Chemotherapy

110. Antibody Responses to <i>Fusobacterium nucleatum</i> Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer. (PubMed)

Antibody Responses to <i>Fusobacterium nucleatumi> Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer. There is a lack of prospective data on the potential association of Fusobacterium nucleatum (F. nucleatum) and colorectal cancer risk. In this study, we assessed whether antibody responses to F. nucleatum are associated with colorectal cancer risk in prediagnostic serum samples in the European Prospective Investigation into Nutrition (...) and Cancer (EPIC) cohort.We applied a multiplex serology assay to simultaneously measure antibody responses to 11 F. nucleatum antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI).We observed neither a statistically significant colorectal cancer risk association for antibodies to individual F. nucleatum proteins nor for combined positivity to any

2019 Cancer Epidemiology & Biomarkers and Prevention

111. Serologic Profile of Antiparietal Cell Antibodies, Pepsinogens, and <i>H. pylori</i> and Risk of Upper Gastrointestinal Cancer: A Nested Case-Control Study in China. (PubMed)

Serologic Profile of Antiparietal Cell Antibodies, Pepsinogens, and <i>H. pylorii> and Risk of Upper Gastrointestinal Cancer: A Nested Case-Control Study in China. Autoimmune gastritis is understudied and possibly associated with gastric noncardia adenocarcinoma (GNCA) and esophageal squamous cell carcinoma (ESCC) in Western populations when it presents as pernicious anemia.A nested case-control study within a Chinese cohort included 100 ESCC, 200 gastric cardia adenocarcinoma (GCA), and 200 (...) GNCA cases diagnosed between 1986 and 2001 and 400 controls. Serostatus of antiparietal cell antibodies (APCA), Helicobacter pylori antibodies, and pepsinogens were measured using commercial kits and serum collected at baseline. We used logistic regression to calculate odds ratios (OR) and 95% confidence interval (CI) for associations between serologic biomarkers and cancer risk adjusted for numerous potential confounders.There was an average interval of 8 years between baseline blood draw

2019 Cancer Epidemiology & Biomarkers and Prevention

112. Antibody Responses to <i>Plasmodium falciparum</i> and <i>Plasmodium vivax</i> and Prospective Risk of <i>Plasmodium</i> spp. Infection Postpartum. (PubMed)

Antibody Responses to <i>Plasmodium falciparumi> and <i>Plasmodium vivaxi> and Prospective Risk of <i>Plasmodiumi> spp. Infection Postpartum. AbstractPostpartum women may have an altered susceptibility to Plasmodium falciparum and Plasmodium vivax. The relationship between naturally acquired malarial immunity and susceptibility to malaria postpartum is yet to be determined. IgG levels were measured against P. falciparum and P. vivax antigens from delivery in 201 postpartum and 201 (...) nonpregnant controls over 12 weeks. Associations between time-varying antibody levels and time to first microscopically confirmed species-specific infection were determined by Cox regression. Associations between antibody levels and prospective risk of Plasmodium infection were similar in postpartum and control women. A 2-fold increase in P. falciparum antibody levels was associated with increased prospective risk of P. falciparum infection (hazard ratio [HR] range = 1.37-1.94). Antibody levels against

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2017 American Journal of Tropical Medicine & Hygiene

113. <i>Porphyromonas gingivalis</i> experimentally induces periodontis and an anti-CCP2-associated arthritis in the rat. (PubMed)

<i>Porphyromonas gingivalisi> experimentally induces periodontis and an anti-CCP2-associated arthritis in the rat. Association between periodontal disease (PD) and rheumatoid arthritis (RA) has been extensively described, but direct evidence of causal involvement of PD in RA is missing. We investigated the priming role of oral Porphyromonas gingivalis (P. gingivalis) in PD and subsequent RA and we assessed biomarkers of bone resorption and arthritis development in rats. METHODS : Lewis rats (...) were orally exposed to either P. gingivalis, Prevotella intermedia or control gel for 1 month and then followed for 8 months. The onset and development of PD was assessed by serology, gingivitis severity and micro-CT (µCT). We investigated arthritis development using circulating proinflammatory markers, anticyclic citrullinated peptide (CCP), anticitrullinated protein antibody (ACPA), ankle histology and µCT. RESULTS : PD was only observed in the P. gingivalis treated rats, as early as 1 month

2019 Annals of the rheumatic diseases

114. Multi-mechanistic monoclonal antibodies targeting <i>S. aureus</i> α-toxin and clumping factor A: Activity and efficacy comparisons of a mAb combination and an engineered bispecific antibody approach. (PubMed)

Multi-mechanistic monoclonal antibodies targeting <i>S. aureusi> α-toxin and clumping factor A: Activity and efficacy comparisons of a mAb combination and an engineered bispecific antibody approach. Secreted alpha-toxin and surface-localized clumping factor A (ClfA) are key virulence determinants in Staphylococcus aureus bloodstream infections. We previously demonstrated that prophylaxis with a multimechanistic monoclonal antibody (MAb) combination against alpha-toxin (MEDI4893*) and ClfA (...) (11H10) provided greater strain coverage and improved efficacy in an S. aureus lethal bacteremia model. Subsequently, 11H10 was found to exhibit reduced affinity and impaired inhibition of fibrinogen binding to ClfA002 expressed by members of a predominant hospital-associated methicillin-resistant S. aureus (MRSA) clone, ST5. Consequently, we identified another anti-ClfA MAb (SAR114) from human tonsillar B cells with >100-fold increased affinity for three prominent ClfA variants, including ClfA002

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2017 Antimicrobial Agents and Chemotherapy

116. An Anti-Human Lutheran Glycoprotein Phage Antibody Inhibits Cell Migration on Laminin-511: Epitope Mapping of the Antibody. (PubMed)

An Anti-Human Lutheran Glycoprotein Phage Antibody Inhibits Cell Migration on Laminin-511: Epitope Mapping of the Antibody. The Lutheran glycoprotein (Lu), also known as basal cell adhesion molecule (B-CAM), is an Ig superfamily (IgSF) transmembrane receptor for laminin α5. Although Lu is not present in normal hepatocytes, its expression is significantly increased in hepatocellular carcinoma (HCC). In this study, we isolated thirteen phage antibodies to Lu from a phage library of peripheral (...) blood from HCC patients, suggesting that these patients produced autoantibodies against endogenous Lu. To characterize the phage antibodies, we determined the Lu domains they recognize. The extracellular domain of Lu contains five IgSF domains, D1-D2-D3-D4-D5. The epitope of one phage antibody (A7) was localized to the D5 domain. The other phage antibodies recognized the D2 domain, which is also recognized by a function blocking mouse monoclonal antibody. One of the antibodies to D2 (C7) inhibited

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2017 PLoS ONE

117. Correction: Development and application of a Bacillus anthracis protective antigen domain-1 in-house ELISA for the detection of anti-protective antigen antibodies in cattle in Zambia. (PubMed)

Correction: Development and application of a Bacillus anthracis protective antigen domain-1 in-house ELISA for the detection of anti-protective antigen antibodies in cattle in Zambia. [This corrects the article DOI: 10.1371/journal.pone.0205986.].

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2019 PLoS ONE

118. Anti-Ro antibodies and complete heart block in adults with Sjögren’s syndrome (PubMed)

Anti-Ro antibodies and complete heart block in adults with Sjögren’s syndrome There are emerging case reports worldwide of complete heart block in adults who test positive for anti-Ro antibodies and the underlying primary Sjögren's syndrome (pSS). The association between fetal/congenital cardiac abnormalities and transplacental transfer of anti-Ro antibodies is well established; there is, however, an ongoing debate about the underlying mechanism of activity of these antibodies in the cardiac (...) tissue. In the past, maternal cardiac tissue was believed to be resistant to these pathogenic effects. This case highlights the need to change our understanding of how these antibodies cause adverse arrhythmogenic cardiac effects in adults. We present the case of a 44-year-old female with pSS and positive anti-Ro autoantibodies, who was diagnosed with autoimmune-induced complete heart block after presenting with dizziness and palpitations. She required insertion of a permanent cardiac pacemaker

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2018 European journal of rheumatology

119. Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway. (PubMed)

Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway. Lenvatinib is a multiple receptor tyrosine kinase inhibitor targeting mainly vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) receptors. We investigated the immunomodulatory activities of lenvatinib in the tumor microenvironment and its mechanisms of enhanced antitumor activity when combined (...) with a programmed cell death-1 (PD-1) blockade. Antitumor activity was examined in immunodeficient and immunocompetent mouse tumor models. Single-cell analysis, flow cytometric analysis, and immunohistochemistry were used to analyze immune cell populations and their activation. Gene co-expression network analysis and pathway analysis using RNA sequencing data were used to identify lenvatinib-driven combined activity with anti-PD-1 antibody (anti-PD-1). Lenvatinib showed potent antitumor activity

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2019 PLoS ONE

120. Introduction of the YTE mutation into the non-immunogenic HIV bnAb PGT121 induces anti-drug antibodies in macaques. (PubMed)

Introduction of the YTE mutation into the non-immunogenic HIV bnAb PGT121 induces anti-drug antibodies in macaques. Recombinant antibodies play increasingly important roles as immunotherapeutic treatments for human cancers as well as inflammatory and infectious diseases and have revolutionized their management. In addition, their therapeutic potential may be enhanced by the introduction of defined mutations in the crystallizable fragment (Fc) domains eg YTE (M252Y/S254T/T256E) and LS (M428L (...) 5mg/kg subcutaneous (SC) injections in naïve macaques of the HIV bnAb PGT121 and its PGT121-YTE mutant, both produced in plants, have been compared towards prolonging efficacy. Induction of anti-drug/anti-idiotypic antibodies (ADA, anti-id) has been monitored using both binding ELISAs and more functional inhibition of virus neutralization (ID50) assays. Timing of the anti-Id responses and their impact on pharmacokinetic profiles (clearance) and efficacy (protection) have also been assessed

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2019 PLoS ONE

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