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SARS-CoV-2 Peptide Bioconjugates Designed for Antibody Diagnostics.

Bioconjug Chem 2021 Jun 28. Epub 2021 Jun 28.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow 117997, Russian Federation.

In the near future, the increase in the number of required tests for COVID-19 antibodies is expected to be many hundreds of millions. Obviously, this will be done using a variety of analytical methods and using different antigens, including peptides. In this work, we compare three method variations for detecting specific immunoglobulins directed against peptides of approximately 15-aa of the SARS-CoV-2 spike protein. Read More

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Easy Surface Functionalization and Bioconjugation of Peptides as Capture Agents of a Microfluidic Biosensing Platform for Multiplex Assay in Serum.

Bioconjug Chem 2021 Jun 11. Epub 2021 Jun 11.

Center for Advanced Biomaterials for [email protected], Istituto Italiano di Tecnologia (IIT), Largo Barsanti e Matteucci 53, 80125 Naples, Italy.

The development of assays for protein biomarkers in complex matrices is a demanding task that still needs implementation of new approaches. Antibodies as capture agents have been largely used in bioassays but their low stability, low-efficiency production, and cross-reactivity in multiplex approaches impairs their larger applications. Instead, synthetic peptides, even with higher stability and easily adapted amino acid sequences, still remain largely unexplored in this field. Read More

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Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study.

Lancet Oncol 2021 06 11;22(6):836-847. Epub 2021 May 11.

Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia; Royal North Shore Hospital, Sydney, NSW, Australia; Mater Hospital, Sydney, NSW, Australia. Electronic address:

Background: Anti-PD-1 therapy (hereafter referred to as anti-PD-1) induces long-term disease control in approximately 30% of patients with metastatic melanoma; however, two-thirds of patients are resistant and will require further treatment. We aimed to determine the efficacy and safety of ipilimumab plus anti-PD-1 (pembrolizumab or nivolumab) compared with ipilimumab monotherapy in patients who are resistant to anti-PD-(L)1 therapy (hereafter referred to as anti-PD-[L]1).

Methods: This multicentre, retrospective, cohort study, was done at 15 melanoma centres in Australia, Europe, and the USA. Read More

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Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial.

Lancet Oncol 2021 05 12;22(5):655-664. Epub 2021 Apr 12.

EORTC Headquarters, Brussels, Belgium.

Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 trial in patients with resected, high-risk stage III melanoma demonstrated improved recurrence-free survival with adjuvant pembrolizumab compared with placebo (hazard ratio 0·57 [98·4% CI 0·43-0·74]; p<0·0001). This study reports the results from the health-related quality-of-life (HRQOL) exploratory endpoint.

Methods: This double-blind, randomised, controlled, phase 3 trial was done at 123 academic centres and community hospitals across 23 countries. Read More

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Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial.

Lancet Oncol 2021 05 12;22(5):643-654. Epub 2021 Apr 12.

EORTC Headquarters, Brussels, Belgium.

Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43-0·74], p<0·0001) compared with placebo, leading to its approval in the USA and Europe. This report provides the final results for the secondary efficacy endpoint, distant metastasis-free survival and an update of the recurrence-free survival results. Read More

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IL-6 modulation for COVID-19: the right patients at the right time?

J Immunother Cancer 2021 04;9(4)

Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Science and Medical Center; Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

The ongoing pandemic caused by the novel coronavirus SARS-CoV-2 has disrupted the global economy and strained healthcare systems to their limits. After the virus first emerged in late 2019, the first intervention that demonstrated significant reductions in mortality for severe COVID-19 in large-scale trials was corticosteroids. Additional options that may reduce the burden on the healthcare system by reducing the number of patients requiring intensive care unit support are desperately needed, yet no therapy has conclusively established benefit in randomized studies for the management of moderate or mild cases of disease. Read More

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A novel vaccine adjuvant based on straight polyacrylate potentiates vaccine-induced humoral and cellular immunity in cynomolgus macaques.

Hum Vaccin Immunother 2021 07 10;17(7):2336-2348. Epub 2021 Jan 10.

Sanofi Pasteur, Research & Development Department, Marcy L'Etoile, France.

Adjuvants are central to the efficacy of subunit vaccines. Although several new adjuvants have been approved in human vaccines over the last decade, the panel of adjuvants in licensed human vaccines remains small. There is still a need for novel adjuvants that can be safely used in humans, easy to source and to formulate with a wide range of antigens and would be broadly applicable to a wide range of vaccines. Read More

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Serum CD73 is a prognostic factor in patients with metastatic melanoma and is associated with response to anti-PD-1 therapy.

J Immunother Cancer 2020 12;8(2)

Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Campania, Italy

Background: Inhibitors of immune checkpoint programmed cell death protein 1 (PD-1) receptor on T cells have shown remarkable clinical outcomes in metastatic melanoma. However, most patients are resistant to therapy. Production of extracellular adenosine, via CD73-mediated catabolism of AMP, contributes to suppress T-cell-mediated responses against cancer. Read More

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December 2020

Wavelength-Tunable Optical Fiber Localized Surface Plasmon Resonance Biosensor a Diblock Copolymer-Templated Nanorod Monolayer.

ACS Appl Mater Interfaces 2020 Nov 2;12(45):50929-50940. Epub 2020 Nov 2.

College of Physics, Dalian University of Technology, Dalian 116024, China.

Well-dispersed and dense layers of gold nanorods (AuNRs) on optical fibers are shown to regulate the longitudinal peak wavelength and enhance the sensing performances of localized surface plasmon resonance (LSPR) biosensors. A simple self-assembly method relying on a brush-like monolayer of poly(styrene)--poly(acrylic acid) (PS--PAA) diblock copolymer was used to immobilize AuNRs with various aspect ratios from 2.33 to 4. Read More

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November 2020

The Great Debate at 'Immunotherapy Bridge', Naples, December 5, 2019.

J Immunother Cancer 2020 08;8(2)

Early Phase Clinical Trials Program, Developmental Therapeutics Program, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.

As part of the 2019 Immunotherapy Bridge congress (December 4-5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practice, whether antibody-dependent cellular cytotoxicity is important in the mode of action of anticytotoxic T-lymphocyte-associated protein 4 antibodies, whether the brain is immunologically unique or just another organ, the role of microbiome versus nutrition in affecting responses to immunotherapy, and whether chemotherapy is immunostimulatory or immunosuppressive. Discussion of these important topics are summarized in this report. Read More

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Outcomes and biomarker analyses among patients with COVID-19 treated with interleukin 6 (IL-6) receptor antagonist sarilumab at a single institution in Italy.

J Immunother Cancer 2020 08;8(2)

Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy

Background: The inflammatory pathology observed in severe COVID-19 disease caused by the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by elevated serum levels of C reactive protein (CRP) and cytokines, including interferon gamma, interleukin 8 (IL-8), and interleukin 6 (IL-6). Initial reports from the outbreak in Italy, China and the USA have provided anecdotal evidence of improved outcomes with the administration of anti-IL-6 agents, and large-scale trials evaluating these therapies are ongoing.

Study Description: In this retrospective case series, clinical outcomes and correlates of response to treatment with the IL-6 receptor antagonist sarilumab are described for 15 patients with COVID-19 from a single institution in Southern Italy. Read More

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Lateral flow immunostrips for the sensitive and rapid determination of 8-hydroxy-2'-deoxyguanosine using upconversion nanoparticles.

Mikrochim Acta 2020 06 9;187(7):377. Epub 2020 Jun 9.

Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, 710062, People's Republic of China.

Lateral flow immunostrips were newly designed and a sensitive and rapid fluorometric method for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a model target of small biomarker molecules was developed. The upconversion nanoparticles (UCNPs, NaYF4:Yb/Er core, and polyacrylic acid (PAA)-modified shell, size ~ 39 nm, excitation wavelength = 980 nm; emission wavelength = 540 nm) were employed as fluorescence signal material. The 8-OHdG antibody (Ab) was taken as the recognition probe while UCNP-labeled Ab was taken as the signal probe. Read More

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Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma.

J Immunother Cancer 2020 06;8(1)

Center for Immuno-Oncology, University Hospital of Siena, Instituto Toscano Tumori, Siena, Italy.

Background: We have previously reported significantly longer overall survival (OS) with ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with advanced melanoma, with higher incidences of adverse events (AEs) at 10 mg/kg. This follow-up analysis reports a 5-year update of OS and safety.

Methods: This randomized, multicenter, double-blind, phase III trial included patients with untreated or previously treated unresectable stage III or IV melanoma. Read More

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Efficacy of dupilumab in atopic comorbidities associated with moderate-to-severe adult atopic dermatitis.

Allergy 2020 10 18;75(10):2653-2661. Epub 2020 May 18.

Dermatology Unit, Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.

Background: Dupilumab is an anti-IL-4Rα antibody used in the treatment of patients with moderate-to-severe atopic dermatitis (msAD). This study explored the potential benefit of dupilumab in perennial allergic rhinoconjunctivitis (PAR) and perennial allergic asthma (PAA) caused by indoor allergens in adults with msAD.

Methods: This multicentric, prospective, observational, real-life study included adult patients with msAD who had been treated with dupilumab in 16 Italian care centres. Read More

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October 2020

The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response.

J Immunother Cancer 2020 05;8(1)

Istituto Nazionale Tumori IRCCS Fondazione 'G. Pascale', Napels, Italy

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as 'cytokine storm'. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Read More

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Ultramarine blue nanoparticles as a label for immunochromatographic on-site determination of ractopamine.

Mikrochim Acta 2020 04 23;187(5):285. Epub 2020 Apr 23.

School of Engineering, Westlake University, 18 Shilongshan Road, Hangzhou, 310024, China.

A competitive immunochromatographic assay (ICA) is presented and used for on-site determination of ractopamine (RAC). Ultramarine blue nanoparticles were directly separated from ultramarine blue industrial products by centrifugation (< 10,000 rpm and > 4000 rpm) and used as visible labels in ICAs. The ultramarine blue nanoparticles were coated by polyacrylic acid (PAA), which provides carboxyl groups on the surface of ultramarine blue nanoparticles. Read More

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Polyacrylic acid based plasma fractionation for the production of albumin and IgG: Compatibility with existing commercial downstream processes.

Biotechnol Bioeng 2020 04 23;117(4):1072-1081. Epub 2020 Jan 23.

Plasma Product Development Department, CSL Behring (Australia) Pty. Ltd., Broadmeadows, Australia.

Commercial fractionation of human plasma into immunoglobulin- and albumin-rich fractions is often initiated with sequential cold ethanol-based precipitation methods, which have changed little over the past 70 years. The required low temperature (-4 to -8°C) and high concentrations of ethanol 8-40%) necessitate large-scale fixed processing lines, and major capital investment and operating costs. The resulting fractions are then further purified by ethanol based precipitation or chromatographic procedures to obtain the purified final product. Read More

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Physicochemical structure of a polyacrylic acid stabilized nanoparticle alum (nanoalum) adjuvant governs TH1 differentiation of CD4+ T cells.

Nanoscale 2020 Jan 13;12(4):2515-2523. Epub 2020 Jan 13.

Infectious Disease Research Institute, Seattle, WA, USA.

The growing shift to subunit antigen vaccines underscores the need for adjuvants that can enhance the magnitude and quality of immune response. Aluminum salts or alums are the first adjuvants with a long history of clinical use. Alum predominantly induces T helper 2 (TH2) type immunity in animal models, characterized by antibody production with little to no induction of antigen-specific T cells. Read More

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January 2020

A Dual-Targeting Functionalized Graphene Film for Rapid and Highly Sensitive Fluorescence Imaging Detection of Hepatocellular Carcinoma Circulating Tumor Cells.

ACS Appl Mater Interfaces 2019 Dec 21;11(48):44999-45006. Epub 2019 Nov 21.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institutes of Biomedical Sciences , Shandong Normal University , Jinan 250014 , People's Republic of China.

High recurrence and metastasis rates are the major causes of the high mortality of hepatocellular carcinoma (HCC). Circulating tumor cells (CTCs) disseminating into the bloodstream play an essential role in cancer metastasis. However, since HCC-CTCs are extremely rare, limitations of current detection methods impede accurate discerning of HCC-CTCs under complicated biological context. Read More

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December 2019

Enhanced paracellular delivery of vaccine by hydrogel microparticles-mediated reversible tight junction opening for effective oral immunization.

J Control Release 2019 10 26;311-312:50-64. Epub 2019 Aug 26.

Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. Electronic address:

The current conventional injectable vaccines face several drawbacks such as inconvenience and ineffectiveness in mucosal immunization. Therefore, the current development of effective oral vaccines is vital to enable the generation of dual systemic and mucosal immunity. In the present study, we examine the potential of pH-responsive bacterial nanocellulose/polyacrylic acid (BNC/PAA) hydrogel microparticles (MPs) as an oral vaccine carrier. Read More

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October 2019

Gold nanoparticles affect the antioxidant status in selected normal human cells.

Int J Nanomedicine 2019 8;14:4991-5015. Epub 2019 Jul 8.

Radiobiology Research Unit, Interdisciplinary Biosciences, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK.CEN), Mol, Belgium.

This study evaluates the cytotoxicity of AuNPs coated with polyallylamine (AuNPs-PAA) and conjugated or not to the epidermal growth factor receptor (EGFR)-targeting antibody Cetuximab (AuNPs-PAA-Ctxb) in normal human kidney (HK-2), liver (THLE-2) and microvascular endothelial (TIME) cells, and compares it with two cancer cell lines that are EGFR-overexpressing (A431) or EGFR-negative (MDA-MB-453). Conjugation of Cetuximab to AuNPs-PAA increased the AuNPs-PAA-Ctxb interactions with cells, but reduced their cytotoxicity. TIME cells exhibited the strongest reduction in viability after exposure to AuNPs-PAA(±Ctxb), followed by THLE-2, MDA-MB-453, HK-2 and A431 cells. Read More

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September 2019

A multiplexed, indirect enzyme-linked immunoassay for the detection and differentiation of E. coli from other Enterobacteriaceae and P. aeruginosa from other glucose non-fermenters.

J Microbiol Methods 2019 03 29;158:52-58. Epub 2019 Jan 29.

School of Public Health, Division of Infectious Disease and Vaccinology, University of California, Berkeley, CA 94720, USA. Electronic address:

Gram-negative bacteria (GNB) are important causes of community (CA) and hospital (HA)- associated infections. Here we describe the development of an indirect ELISA (I-ELISA), which can be used to detect and differentiate the Enterobacteriaceae Escherichia coli, and glucose non-fermenter Pseudomonas aeruginosa from other GNB species. The I-ELISA utilizes six antibodies for bacterial speciation, which were grouped according to their bacterial targets; Enterobacteriaceae (SL-EntA and CH1810 mAb), Escherichia coli (SL-EcA and 6103-46 mAb), Pseudomonas aeruginosa (SL-PaA and SL-PaB). Read More

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Reprogramming the adjuvant properties of aluminum oxyhydroxide with nanoparticle technology.

NPJ Vaccines 2019 3;4. Epub 2019 Jan 3.

1Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102 USA.

Aluminum salts, developed almost a century ago, remain the most commonly used adjuvant for licensed human vaccines. Compared to more recently developed vaccine adjuvants, aluminum adjuvants such as Alhydrogel are heterogeneous in nature, consisting of 1-10 micrometer-sized aggregates of nanoparticle aluminum oxyhydroxide fibers. To determine whether the particle size and aggregated state of aluminum oxyhydroxide affects its adjuvant activity, we developed a scalable, top-down process to produce stable nanoparticles (nanoalum) from the clinical adjuvant Alhydrogel by including poly(acrylic acid) (PAA) polymer as a stabilizing agent. Read More

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January 2019

Protein nanoparticles with ligand-binding and enzymatic activities.

Int J Nanomedicine 2018 18;13:6637-6646. Epub 2018 Oct 18.

Department of Biophysics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency (FRCC PCM), Moscow, Russia,

Purpose: To develop a general method for NP fabrication from various proteins with maintenance of biological activity.

Methods: A novel general approach for producing protein nanoparticles (NP) by nanoprecipitation of the protein solutions in 1,1,1,3,3,3-hexafluoroisopropanol is described. Protein NP sizes and shapes were analyzed by dynamic light scattering, scanning electron and atomic force microscopy (SEM and AFM). Read More

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December 2018

Protein phosphatase 2A is crucial for sarcomere organization in Caenorhabditis elegans striated muscle.

Mol Biol Cell 2018 08 27;29(17):2084-2097. Epub 2018 Jun 27.

Department of Pathology, Emory University, Atlanta, GA 30322.

Protein phosphatase 2A (PP2A) is a heterotrimer composed of single catalytic and scaffolding subunits and one of several possible regulatory subunits. We identified PPTR-2, a regulatory subunit of PP2A, as a binding partner for the giant muscle protein UNC-89 (obscurin) in Caenorhabditis elegans. PPTR-2 is required for sarcomere organization when its paralogue, PPTR-1, is deficient. Read More

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Freeze-dried matrices for ocular administration of bevacizumab: a comparison between subconjunctival and intravitreal administration in rabbits.

Drug Deliv Transl Res 2018 06;8(3):461-472

Department of Pharmacy, University of Pisa, via Bonanno 33, 56126, Pisa, Italy.

This work was aimed to tune solid matrices for bevacizumab (BVZ) subconjunctival or intravitreal administration in order to prolong drug release, to reduce the number of applications and consequently the side effects. Matrices, with sizes suitable for intravitreal or subconjunctival administration, based on hydroxypropylmethyl cellulose (HPMC), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and polyacrylic acid (PAA) were obtained by freeze-drying of polymeric dispersions either in phosphate buffer solution or water and were sterilized by gamma rays. The matrices were characterized from the technological point of view and evaluated for in vitro release of dextran and BVZ. Read More

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Improving the sensitivity of immunoassays by reducing non-specific binding of poly(acrylic acid) coated upconverting nanoparticles by adding free poly(acrylic acid).

Mikrochim Acta 2018 03 13;185(4):220. Epub 2018 Mar 13.

Department of Biotechnology, University of Turku, Tykistökatu 6A, 20520, Turku, Finland.

Upconverting nanoparticles (UCNPs) are attractive reporters in immunoassays because of their outstanding detectability. However, non-specific binding of antibody-UCNP conjugates on protein coated solid support results in background, which limits the immunoassay sensitivity. Thus, the full potential of UCNPs as reporters cannot be fully exploited. Read More

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Human IgG subclass cross-species reactivity to mouse and cynomolgus monkey Fcγ receptors.

Immunol Lett 2018 05 21;197:1-8. Epub 2018 Feb 21.

Janssen BioTherapeutics, Janssen R&D, 1400 McKean Rd, Spring House, PA, United States.

In therapeutic antibody discovery and early development, mice and cynomolgus monkey are used as animal models to assess toxicity, efficacy and other properties of candidate molecules. As more candidate antibodies are based on human immunoglobulin (IgG) subclasses, many strategies are pursued to simulate the human system in the test animal. However, translation rate from a successful preclinical trial to an approved drug is extremely low. Read More

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Capture and release of cells using a temperature-responsive surface that immobilizes an antibody through DNA duplex formation.

J Biomater Sci Polym Ed 2017 Jul - Aug;28(10-12):1172-1182. Epub 2017 Mar 28.

a Institute of Biomaterials and Bioengineering , Tokyo Medical and Dental University , Tokyo , Japan.

We synthesized a temperature-responsive surface that immobilized an antibody via DNA duplex formation for selective capture and release of target cells. Polyethylene films were modified by grafting poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc)), which were prepared at various ratios of NIPAAm/AAc. The increased hydrophilicity of P(NIPAAm-co-PAA) film with decreased temperature was confirmed by water contact angle measurement. Read More

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February 2018