306,800 results match your criteria Monoclonal Gammopathies of Uncertain Origin


Migraine and Tension-Type Headache.

Semin Neurol 2018 Dec 6;38(6):608-618. Epub 2018 Dec 6.

Department of Neurology, Boston Medical Center, Boston, Massachusetts.

Migraine and tension-type headache (TTH) are common primary disorders that carry significant morbidity and socioeconomic effect. In this article, we will review the epidemiology, presentation, and diagnosis of these disorders. First-line acute treatment for migraine consists of analgesics, triptans, and antiemetics, while nonsteroidal anti-inflammatory drugs are the mainstay treatment for TTH. Read More

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December 2018
2 Reads

PD-1/ PD-L1 blockade as a novel treatment for colorectal cancer.

Biomed Pharmacother 2018 Dec 3;110:312-318. Epub 2018 Dec 3.

Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Colorectal cancer (CRC), as a prominent cause of cancer-related deaths, has historically been notable worldwide and many attempts have been made to raise the overall survival of CRC patients. Immune response has long been a question of great interest in a wide range of fields such as cancer therapies and anti-tumor immunity through checkpoint inhibitors, specifically anti PD-1/ PD-L1 interaction, is a new line of research for treatment of CRC patients. Following the successful development of anti-PD-1 for melanoma, renal cell carcinoma, and non-small cell lung cancer, several clinical trials have been conducted on monoclonal antibodies (MAbs) against PD-1 in CRC. Read More

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December 2018
9 Reads

Bezlotoxumab Use as Adjunctive Therapy with the Third Fecal Microbiota Transplant in Refractory Recurrent Clostridium Difficile Colitis; A Case Report and Concise Literature Review.

Anaerobe 2018 Dec 3. Epub 2018 Dec 3.

ABIM Board Certified in Focused Practice in Hospital Medicine (FPHM), Mercy Clinic Hospitalist, Physician Building, 7301 Rogers Ave, Fort Smith, AR, 72903, United States. Electronic address:

Clostridium difficile is the most commonly reported pathogen to cause nosocomial infections in the United States with a high burden affecting morbidity, mortality and healthcare expenditure. The use of Fecal Microbiota Transplantation (FMT) is one of the current standard therapies for recurrent C. difficile infection (CDIr). Read More

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December 2018
1 Read

CCR5 structural plasticity shapes HIV-1 phenotypic properties.

PLoS Pathog 2018 Dec 6;14(12):e1007432. Epub 2018 Dec 6.

Viral Pathogenesis Unit, Department of Virology, Institut Pasteur, Paris, France.

CCR5 plays immune functions and is the coreceptor for R5 HIV-1 strains. It exists in diverse conformations and oligomerization states. We interrogated the significance of the CCR5 structural diversity on HIV-1 infection. Read More

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December 2018
1 Read

Structural basis for neutralization of cytotoxic abrin by monoclonal antibody D6F10.

FEBS J 2018 Dec 6. Epub 2018 Dec 6.

Department of Physics, Indian Institute of Science, Bengaluru, 560012, India.

Abrin, an extremely cytotoxic Type-II ribosome inactivating protein (RIP), is a potential bio-warfare agent. Abrin A-chain (ABA) depurinates an adenosine of sarcin-ricin loop (SRL) from eukaryotic 28S rRNA thereby arresting protein synthesis and leading to cell death. Monoclonal antibody (mAb) D6F10 is the only known antibody that neutralizes ABA's activity in cell-free systems as well as abrin's toxicity in vitro and in vivo. Read More

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December 2018

Nail Psoriasis: An Updated Review and Expert Opinion on Available Treatments, Including Biologics.

Acta Derm Venereol 2018 Dec 6. Epub 2018 Dec 6.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Massarenti 1, IT-40138 Bologna, Italy.

Nail psoriasis affects 50-79% of patients with skin psoriasis and up to 80% of patients with psoriatic arthritis, and can also represent a negative prognostic factor in individuals with plaque psoriasis. Treatments for nail psoriasis are limited, as nails are often difficult to treat with topical therapies alone, and relapse is common. Among different systemic agents, secukinumab, a fully human monoclonal antibody targeting interleukin (IL)-17A, is the only antibody supported by a trial specifically conducted in patients with nail psoriasis (the TRANSFIGURE trial) and has the longest follow-up available to date. Read More

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December 2018
3 Reads

T-cell Activating Tribodies as a Novel Approach for Efficient Killing of ErbB2-positive Cancer Cells.

J Immunother 2019 Jan;42(1):1-10

Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II.

The Tyrosine Kinase Receptor ErbB2 (HER2) when overexpressed in breast cancer (BC) is associated with poor prognosis. The monoclonal antibody Trastuzumab has become a standard treatment of ErbB2+BC. The antibody treatment has limited efficacy, often meets resistance and induces cardiotoxicity. Read More

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January 2019

Pembrolizumab in the treatment of advanced/metastatic melanoma: a single-center institution experience.

Melanoma Res 2018 Dec 4. Epub 2018 Dec 4.

Melanoma Medical Oncology Unit, Department of Medical Oncology and Hematology.

Pembrolizumab is an anti-programmed cell death-1 monoclonal antibody, currently representing the first-line treatment for advanced melanoma. Apart from registration trials, there is a paucity of data on its effectiveness and safety in a real-world setting. We retrospectively analyzed patients with metastatic melanoma treated at our institution in the context of an Expanded Access Program. Read More

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December 2018

M918: A novel cell penetrating peptide for effective delivery of HIV-1 Nef and Hsp20-Nef proteins into eukaryotic cell lines.

Curr HIV Res 2018 Dec 5. Epub 2018 Dec 5.

Pilot Nano-Biotechnology Department, Pasteur Institute of Iran, Tehran. Iran.

Background: HIV-1 Nef protein is a possible attractive target in development of therapeutic HIV vaccines including protein-based vaccines. The most important disadvantage of protein-based vaccines is their low immunogenicity which can be improved by heat shock proteins (Hsps) as an immunomodulator, and cell penetrating peptides (CPPs) as a carrier.

Methods: In this study, the HIV-1 Nef and Hsp20-Nef proteins were generated in E. Read More

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December 2018
3 Reads

Clinical and biological characteristics of myeloma patients influence response to elotuzumab combination therapy.

J Cancer Res Clin Oncol 2018 Dec 5. Epub 2018 Dec 5.

Division of Hematology and Medical Oncology, Department of Internal Medicine II, University Hospital Würzburg, Oberdürrbacherstraße 6, 97080, Würzburg, Germany.

Based on ELOQUENT-2, combination therapy with the monoclonal antibody elotuzumab was approved for relapsed/refractory multiple myeloma in the US and Europe. However, outside clinical trials, the optimal integration of elotuzumab into the sequence of treatment lines remains to be determined. Therefore, we analyzed safety and efficacy of elotuzumab/immunomodulatory drug combinations in a real-life cohort of 33 patients from our institution. Read More

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December 2018

The mouse-canine chimeric anti-dog podoplanin antibody P38B exerts antitumor activity in mouse xenograft models.

Biochem Biophys Rep 2019 Mar 24;17:23-26. Epub 2018 Nov 24.

Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.

Podoplanin (PDPN) is a type I transmembrane heavily glycosylated sialoglycoprotein that is expressed in normal tissues such as pulmonary type I alveolar cells, renal podocytes, and lymphatic endothelial cells. PDPN overexpression in cancerous tissue is associated with hematogenous metastasis through interactions with the C-type lectin-like receptor 2 (CLEC-2). Previously, we have reported the development of a mouse monoclonal antibody (mAb), PMab-38 (IgG, kappa) against dog PDPN (dPDPN). Read More

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Spotlight on risankizumab and its potential in the treatment of plaque psoriasis: evidence to date.

Psoriasis (Auckl) 2018 13;8:83-92. Epub 2018 Nov 13.

Department of Dermatology, Centro Hospitalar Universitário do Porto, Porto, Portugal,

Psoriasis is a common chronic immune-mediated skin disease, with systemic involvement and significant impact in patients' quality of life. Several highly specific treatments have been developed over the years, such as tumor necrosis factor-α inhibitors, a nonselective IL-23 inhibitor (ustekinumab), and most recently IL-17 inhibitors. Risankizumab is a monoclonal antibody which targets IL-23p19 without binding IL-12. Read More

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November 2018
1 Read

The Efficacy and Safety of Anti-epidermal Growth Factor Receptor Monoclonal Antibodies in Nasopharyngeal Carcinoma: Literature-based Meta-analyses.

J Cancer 2018 31;9(23):4510-4520. Epub 2018 Oct 31.

Department of Radiation Oncology, Sun Yat-sen University Cancer Centre; State Key Laboratory of Oncology in South China; Collaborative Innovation Centre of Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.

Anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs), such as cetuximab and nimotuzumab have been used in the treatment of nasopharyngeal carcinoma (NPC), yet their efficacy and safety are undetermined. : We performed two meta-analyses based on systematic searches of PubMed, EMBASE, the Cochrane Library and SinoMed: comparison 1 (standard therapy plus mAbs vs. standard therapy) and comparison 2 (radiotherapy plus concurrent mAbs vs. Read More

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October 2018
1 Read

The Association of Baseline Serum Tumour Markers with Outcome of Patients with Metastatic Colorectal Cancer Treated with Anti-EGFR Monoclonal Antibodies in the First Line.

J Cancer 2018 20;9(22):4255-4262. Epub 2018 Oct 20.

Department of Oncology and Radiotherapy, Medical School and University Hospital in Pilsen, Charles University, Czech Republic.

The measurement of serum tumour markers is a simple and non-invasive method for assessing the response to systemic therapies in metastatic colorectal cancer (mCRC) and estimation of prognosis. The aim of our retrospective study was to evaluate the association of baseline serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), thymidine kinase (TK) and tissue polypeptide specific antigen (TPS) with outcome of patients with mCRC treated with combination of chemotherapy and monoclonal antibodies against epidermal growth factor receptor (anti-EGFR mAbs) in the first line. In our study, the cohort included 102 patients treated with therapy based on anti-EGFR mAbs between years 2011 and 2017 at Department of Oncology and Radiotherapy, Medical School and University Hospital in Pilsen, Czech Republic. Read More

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October 2018
1 Read

Identification of a HIV Gp41-Specific Human Monoclonal Antibody With Potent Antibody-Dependent Cellular Cytotoxicity.

Front Immunol 2018 16;9:2613. Epub 2018 Nov 16.

AIDS Institute, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.

Antibody-Dependent Cellular Cytotoxicity (ADCC) is a major mechanism of protection against viral infections . Identification of HIV-1-specific monoclonal antibodies (mAbs) with potent ADCC activity may help develop an effective HIV-1 vaccine. In present study, we isolated such human mAb, designated E10, from an HIV-1-infected patient sample by single B cell sorting and single cell PCR. Read More

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November 2018
2 Reads

Patient satisfaction, health care resource utilization, and acute headache medication use with galcanezumab: results from a 12-month open-label study in patients with migraine.

Patient Prefer Adherence 2018 13;12:2413-2424. Epub 2018 Nov 13.

Department of Neurology - Headache and Facial Pain Clinic, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Brussels, Belgium.

Background: Effects of galcanezumab, a monoclonal antibody against calcitonin gene-related peptide, on patient satisfaction, health care resource utilization (HCRU), and acute medication use were evaluated in a long-term, open-label study in patients with migraine.

Methods: Patients with episodic (78.9%) or chronic migraine (21. Read More

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November 2018

A study on screening and antitumor effect of CD55-specific ligand peptide in cervical cancer cells.

Drug Des Devel Ther 2018 13;12:3899-3912. Epub 2018 Nov 13.

Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao 266071, People's Republic of China,

Background: To improve the targeting ability of antitumor drugs, we identified the antigens with high expression on the surface of tumor cells associated with tumor escape, such as the complement regulatory protein CD55 molecule, which is also known as the decay accelerating factor. In this study, phage display technology was used to screen and identify CD55-specific ligand peptide (CD55sp) bound to CD55 molecule on the surface of cervical cancer HeLa cells. We then explored the role of this peptide in inhibiting the growth of cervical cancer cells in vitro. Read More

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November 2018

Risankizumab: an anti-IL-23 antibody for the treatment of psoriasis.

Drug Des Devel Ther 2018 12;12:3879-3883. Epub 2018 Nov 12.

Department of Dermatology, Baylor University Medical Center, Dallas, TX, USA,

Risankizumab, a fully human IgG monoclonal antibody inhibitor of IL-23, is a therapeutic agent currently in late stage development for use in the treatment of moderate-to-severe plaque psoriasis. It is a biologic agent similar to guselkumab and tildrakizumab which targets IL-23 specifically, and has been primarily developed for use in moderate-to-severe psoriasis. USA-based pharmaceutical company Abbvie submitted it for a Biologics License Application to the US Food and Drug Administration (FDA) in April 2018. Read More

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November 2018

An accurate TMT-based approach to quantify and model lysine susceptibility to conjugation via N-hydroxysuccinimide esters in a monoclonal antibody.

Sci Rep 2018 Dec 5;8(1):17680. Epub 2018 Dec 5.

Human Health Therapeutics Research Centre, National Research Council Canada, 6100 Royalmount Ave, Montreal, QC, H4P 2R2, Canada.

Conjugation of small molecules to proteins through N-hydroxysuccinimide (NHS) esters results in a random distribution of small molecules on lysine residues and the protein N-terminus. While mass spectrometry methods have improved characterization of these protein conjugates, it remains a challenge to quantify the occupancy at individual sites of conjugation. Here, we present a method using Tandem Mass Tags (TMT) that enabled the accurate and sensitive quantification of occupancy at individual conjugation sites in the NIST monoclonal antibody. Read More

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December 2018

ANTIBODY-MEDIATED PROTECTIVE MECHANISMS INDUCED BY A TRIVALENT PARAINFLUENZA-VECTORED EBOLAVIRUS VACCINE.

J Virol 2018 Dec 5. Epub 2018 Dec 5.

Department of Pathology, University of Texas Medical Branch, Galveston, TX

Ebolaviruses Zaire (EBOV), Bundibugyo (BDBV) and Sudan (SUDV) cause human disease with high case fatality rates. Experimental monovalent vaccines, which all utilize the sole envelope glycoprotein (GP), do not protect against heterologous ebolaviruses. Human parainfluenza virus type 3-vectored vaccines offer benefits including needle-free administration and induction of mucosal responses in the respiratory tract. Read More

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December 2018

A human-derived antibody targets misfolded SOD1 and ameliorates motor symptoms in mouse models of amyotrophic lateral sclerosis.

Sci Transl Med 2018 Dec;10(470)

Neurimmune AG, 8952 Schlieren, Switzerland.

Mutations in the gene encoding superoxide dismutase 1 (SOD1) lead to misfolding and aggregation of SOD1 and cause familial amyotrophic lateral sclerosis (FALS). However, the implications of wild-type SOD1 misfolding in sporadic forms of ALS (SALS) remain unclear. By screening human memory B cells from a large cohort of healthy elderly subjects, we generated a recombinant human monoclonal antibody (α-miSOD1) that selectively bound to misfolded SOD1, but not to physiological SOD1 dimers. Read More

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December 2018
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Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial.

Lancet Oncol 2018 Nov 30. Epub 2018 Nov 30.

University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Axicabtagene ciloleucel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. In the previous analysis of the ZUMA-1 registrational study, with a median follow-up of 15·4 months (IQR 13·7-17·3), 89 (82%) of 108 assessable patients with refractory large B-cell lymphoma treated with axicabtagene ciloleucel achieved an objective response, and complete responses were noted in 63 (58%) patients. Here we report long-term activity and safety outcomes of the ZUMA-1 study. Read More

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November 2018

Exploring Protein-Inorganic Hybrid Nanoflowers and Immune Magnetic Nanobeads to Detect Typhimurium.

Nanomaterials (Basel) 2018 Dec 4;8(12). Epub 2018 Dec 4.

Key Laboratory of Agricultural Information Acquisition Technology, Ministry of Agriculture, China Agricultural University, Beijing 100083, China.

Early screening of pathogenic bacteria is key to preventing and controlling outbreaks of foodborne diseases. In this study, protein-inorganic hybrid nanoflowers were synthesized for signal amplification and used with a calcium ion selective electrode (Ca-ISE) to establish a new enzyme-free assay for rapid and sensitive detection of . Calcium hydrophosphate crystals were first conjugated with polyclonal antibodies against to synthesize immune calcium nanoflowers (CaNFs), and streptavidin modified magnetic nanobeads (MNBs) were conjugated with biotinylated monoclonal antibodies against to form immune MNBs. Read More

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December 2018
1 Read

Simple and Novel Assay of the Host-Guest Complexation of Homocysteine with Cucurbit[7]uril.

J Microbiol Biotechnol 2018 Nov 28. Epub 2018 Nov 28.

Department of Applied Chemistry, Kumoh National Institute of Technology, Gumi 39177, Korea.

This paper introduces three ways to determine host-guest complexation of cucurbit[7]uril (CB[7]) with homocysteine (Hcy). After preincubating Hcy and cysteine (Cys) with CB[7], Ellman's reagent (DTNB) was used to detect Hcy and Cys. Only Cys reacted with DTNB and Hcy gave a retarded color change. Read More

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November 2018

Treatment of Osteoporosis, with a Focus on 2 Monoclonal Antibodies.

Med Sci Monit 2018 Dec 3;24:8758-8766. Epub 2018 Dec 3.

Department of Laser Medicine, Chinese People's Liberation Army General Hospital, Beijing, China (mainland).

Osteoporosis is a common skeletal disease characterized by bone loss and subsequent increased risk of fragility fractures. Recent advances in our mechanistic understanding of molecular communications among osteoblasts, osteoclasts, and osteocytes give insight into the important roles of the canonical Wnt/β-catenin pathway and the RANK/RANKL/OPG pathway in the process of bone remodeling. Due to the translation of the canonical Wnt/β-catenin pathway and the RANK/RANKL/OPG pathway in the regulation of osteoblasts and osteoclasts, new targets have been studied in recent years, such as sclerostin and receptor activator of NF-κB ligand (RANKL). Read More

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December 2018
7 Reads

Impact of secukinumab on endothelial dysfunction and other cardiovascular disease parameters in psoriasis patients over 52 weeks.

J Invest Dermatol 2018 Nov 30. Epub 2018 Nov 30.

Kardiologie 1, and DZHK Standort Rhein-Main, Universitätsmedizin Mainz, Mainz, Germany.

Psoriasis increases the risk of cardiovascular (CV) disease. Secukinumab, a fully human monoclonal antibody against IL-17A, shows significant efficacy in psoriasis, but effects on CV markers are unknown. CARIMA was a 52-week, randomized, double-blind, placebo-controlled, exploratory trial in patients with moderate to severe plaque psoriasis without clinical CV disease. Read More

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November 2018

One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study.

J Bone Miner Res 2018 Dec 3. Epub 2018 Dec 3.

Amgen Inc., Thousand Oaks, CA, USA.

Romosozumab, a humanized monoclonal antibody that binds and inhibits sclerostin, has the dual effect of increasing bone formation and decreasing bone resorption. As previously reported in the pivotal FRActure study in postmenopausal woMen with ostEoporosis (FRAME), women with a T-score of ≤ -2.5 at the total hip or femoral neck received subcutaneous placebo or romosozumab once monthly for 12 months, followed by open-label subcutaneous denosumab every 6 months for an additional 12 months. Read More

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December 2018
1 Read

Omalizumab for chronic rhinosinusitis.

Medwave 2018 Nov 23;18(7):e7347. Epub 2018 Nov 23.

Proyecto Epistemonikos, Santiago, Chile; Departamento de Otorrinolaringología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. Email: Address: Centro Evidencia UC, Pontificia Universidad Católica de Chile, Diagonal Paraguay 476, Santiago, Chile.

Introduction: Chronic rhinosinusitis is a high prevalence chronic inflammatory disease that involves nasal mucosa and paranasal sinuses. Immunoglobulin E is an inflammatory mediator that plays an etiopathogenic role in this condition, so omalizumab, an anti-immunoglobulin E monoclonal antibody, might be a therapeutic alternative.

Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. Read More

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November 2018

Autologous canine immunotherapy: short-time generated dendritic cells loaded with canine transmissible venereal tumor-whole lysate.

Immunopharmacol Immunotoxicol 2018 Dec 3:1-7. Epub 2018 Dec 3.

a Virology and Immunology Laboratory, Biological Science Faculty , Autonomous University of Nuevo León (AUNL) , San Nicolás de los Garza , México.

Objective: The aim of the present study was to evaluate the therapeutic potential of autologous DCs loaded with whole tumor cell lysate of CTVT generated under a simplified and rapid procedure in vitro production process, in a vulvar submucosal model of CTVT in dogs.

Materials And Methods: We generated a model of intravulvar CTVT in dogs. A CTVT lysate antigen was prepared according to the method of 1-butanol and after administered with complete Freund's adjuvant via subcutaneous in female healthy dogs and challenge with CTVT cells to corroborate the immunogenicity. Read More

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December 2018
1 Read

Monoclonal antibody against human Tim-3 enhances antiviral immune response.

Scand J Immunol 2018 Dec 1:e12738. Epub 2018 Dec 1.

Institute of Beijing Brain Sciences, Beijing, 100850, China.

T cell immunoglobulin and mucin domain protein 3 (Tim-3) is an immune checkpoint inhibitor in T cells and innate immune cells. The deregulated upregulation of Tim-3 is related to immune exhaustion in tumor and viral infection. To overcome Tim-3-mediated immune tolerance, we developed a novel monoclonal antibody against human Tim-3 (L3G) and investigated its roles in inhibiting Tim-3 signaling and overcoming immune tolerance in T cells and monocytes/macrophages. Read More

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December 2018

Plant-derived secretory component forms secretory IgA with shiga toxin 1-specific dimeric IgA produced by mouse cells and whole plants.

Plant Cell Rep 2018 Nov 30. Epub 2018 Nov 30.

Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Shizuoka, 422-8526, Japan.

Key Message: A key module, secretory component (SC), was efficiently expressed in Arabidopsis thaliana. The plant-based SC and immunoglobulin A of animal or plant origin formed secretory IgA that maintains antigen-binding activity. Plant expression systems are suitable for scalable and cost-effective production of biologics. Read More

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November 2018

Assessing the effects of long-term osteoporosis treatment by using conventional spine radiographs: results from a pilot study in a sub-cohort of a large randomized controlled trial.

Skeletal Radiol 2018 Dec 1. Epub 2018 Dec 1.

Department of Internal Medicine, Division of Endocrinology & Diabetology, Medical University of Graz, Auenbruggerpl. 15, 8036, Graz, Austria.

Objective: To evaluate the clinical applicability of a software tool developed to extract bone textural information from conventional lumbar spine radiographs, and to test it in a subset of postmenopausal women treated for osteoporosis with the fully human monoclonal antibody denosumab.

Methods: The software was developed based on the principles of a fractal model using pixel grey-level variations together with a specific machine-learning algorithm. The obtained dimensionless parameter, termed bone structure value (BSV), was then tested and compared to bone mineral density (BMD) in a sub-cohort of postmenopausal women with osteoporosis who were treated with the monoclonal antibody denosumab, within the framework of a large randomized controlled trial and its open-label extension phase. Read More

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December 2018

Immunomodulators in chronic rhinosinusitis.

World J Otorhinolaryngol Head Neck Surg 2018 Sep 10;4(3):186-192. Epub 2018 Nov 10.

Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Objective: To provide new insight into how chronic rhinosinusitis (CRS) is conceptualized and treated with a focus on immunomodulator therapy.

Data Sources: Pubmed, Medline, and Embase.

Methods: A current review of the evidence is provided for immunomodulators investigated for treatment of CRS with nasal polyps (CRSwNP). Read More

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September 2018

Approach to evaluating tumor mutational burden in routine clinical practice.

Transl Lung Cancer Res 2018 Dec;7(6):678-681

Foundation Medicine, Inc., Cambridge, MA, USA.

Immune checkpoint inhibition with monoclonal antibodies has emerged as a promising therapeutic approach but in most tumor types responses are unpredictable and observed in a minority of treated patients. Positive and negative predictive biomarkers for efficacy of these costly drugs are desperately needed. Immunohistochemistry (IHC) for programmed death ligand (PD-L1) expression in tumor and inflammatory infiltrate has emerged as one predictive biomarker of some value. Read More

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December 2018
1 Read

Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma.

Front Immunol 2018 16;9:2431. Epub 2018 Nov 16.

Department of Haematooncology, University Hospital Ostrava, Ostrava, Czechia.

The treatment of cancer, especially of various types of solid tumors, has been revolutionized by the blockade of the PD-1/PD-L1 pathway by immune checkpoint inhibitors. Their success amongst hematologic malignancies, however, has been limited so far to the treatment of classic Hodgkin's lymphoma, which portrays a typical overexpression of PD-1 ligands (PD-L1, PD-L2) as a consequence of changes in chromosome 9p24.1. Read More

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November 2018
1 Read

[Analysis of Time-to-onset and Onset-pattern of Interstitial Lung Disease after the Administration of Monoclonal Antibody Agents].

Yakugaku Zasshi 2018 ;138(12):1587-1594

Faculty of Pharmaceutical Sciences, Himeji Dokkyo University.

The aim of this study has been to investigate the time-to-onset and onset-pattern of drug-induced interstitial lung disease (DILD) after the administration of monoclonal antibodies through the use of the spontaneous adverse reaction reporting system of the Japanese Adverse Drug Event Report database. DILD datasets for adalimumab, bevacizumab, cetuximab, denosumab, golimumab, infliximab, nivolumab, panitumumab, pembrolizumab, tocilizumab, and trastuzumab were used to calculate the median time-to-onset of DILD, as well as the Weibull distribution parameters. The median time-to-onset of DILD for pembrolizumab and infliximab was within 1 month. Read More

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January 2018

ANGPTL3 Inhibitors - Their Role in Cardiovascular Disease Through Regulation of Lipid Metabolism.

Circ J 2018 Nov 30. Epub 2018 Nov 30.

Department of Internal Medicine, Evangelismos General Hospital.

Elevated plasma lipid levels are linked to atherosclerosis, a hallmark for coronary artery disease (CAD), documented by animal studies as well as angiographic and clinical studies. The ability to treat hyperlipidemia through lifestyle changes and lipid-lowering agents has been related to the slow progression of atherosclerosis and decreased incidence of major coronary events. Angiopoietin-like proteins (ANGPTLs) are a family of secreted glycoproteins expressed in the liver that share common domain characteristics with angiopoietins, the main regulators of angiogenesis. Read More

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November 2018

Complement-driven anemia: more than just paroxysmal nocturnal hemoglobinuria.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):371-376

Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

Atypical hemolytic uremic syndrome (aHUS); hemolysis, elevated liver function tests, and low platelets syndrome; and transplant-associated thrombotic microangiopathy are related conditions, in that many patients harbor germline heterozygous mutations in genes that regulate the alternative pathway of complement (APC). Penetrance is variable because development of clinically significant disease appears to require supervention of a process such as inflammation. Complement activation on the endothelial surfaces leads to endothelial damage, platelet consumption, microthrombi, and a mechanical hemolytic anemia with schistocytes. Read More

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November 2018

Hypereosinophilic syndrome: approach to treatment in the era of precision medicine.

Authors:
Amy Klion

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):326-331

Human Eosinophil Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Hypereosinophilic syndromes (HESs) are a heterogeneous group of rare disorders characterized by peripheral eosinophilia and eosinophilic end organ complications. Conventional therapies, including glucocorticoids and cytotoxic and immunomodulatory agents, have variable efficacy and significant toxicity. Although the recent development of agents that target eosinophils, including tyrosine kinase inhibitors and monoclonal antibodies, provides the possibility of more effective, less toxic approaches to treatment of HES, there are little available data to guide their use in these conditions. Read More

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November 2018

Where to start? Upfront therapy for follicular lymphoma in 2018.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):185-188

Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.

The initial approach to the management of follicular lymphoma (FL) is challenging for patients and physicians. Most FL patients present with minimal symptoms; given the lack of a survival benefit to early treatment in this population, a period of observation without therapy is often appropriate. Once there is disease progression beyond low-tumor-burden criteria or symptoms prompting intervention, patients may be considered for an array of potential treatment options. Read More

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November 2018
3 Reads

Case-based roundtable on treatment approach for young, fit, newly diagnosed multiple myeloma patients.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):103-109

Johns Hopkins University School of Medicine, Baltimore, MD.

With the advent new proteasome inhibitors (carfilzomib, ixazomib), new immune-modulatory drugs (pomalidomide), and new monoclonal antibodies (elotuzimab, daratumumab) as approved treatments for myeloma, the therapeutic landscape for this disease has changed. In this chapter, using a case-based approach, I will provide a personal guide of how I approach myeloma therapy in a transplant eligible patient in 2018. Read More

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November 2018
1 Read

No free rides: management of toxicities of novel immunotherapies in ALL, including financial.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):25-34

Division of Hematology and Bone Marrow Transplant, Mayo Clinic, Rochester, MN.

Therapeutic options for acute lymphoblastic leukemia, especially in the relapsed/refractory setting, have expanded significantly in recent times. However, this comes at the cost of toxicities: medical as well as financial. We highlight some of the unique toxicities associated with the novel agents to apprise our readers about what to expect, how to recognize them, and how to manage these toxicities. Read More

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November 2018

Antibody-based therapies in patients with acute lymphoblastic leukemia.

Hematology Am Soc Hematol Educ Program 2018 Nov;2018(1):9-15

Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA.

The use of multiagent combination chemotherapy regimens results in cure rates of >90% for children and ∼40% for adults with acute lymphoblastic leukemia (ALL) but is associated with extensive toxicity and disappointingly low efficacy in relapsed patients. ALL blast cells express several surface antigens, including CD20, CD22, and CD19, which represent valuable targets for immunotherapy. Monoclonal antibodies, antibody-drug conjugates, and bispecific T-cell-engaging antibodies targeting these antigens offer novel mechanisms of action. Read More

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November 2018
2 Reads

Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin (α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders.

Transl Oncol 2018 Nov 29;12(2):368-374. Epub 2018 Nov 29.

Nordic Bioscience A/S, Herlev, Denmark.

Objectives: Remodeling of the extracellular matrix (ECM) is a key event in different lung disorders, such as fibrosis and cancer. The most common cell type in the connective tissue is fibroblasts, which transdifferentiate into myofibroblasts upon activation. All myofibroblasts express α-SMA, which has been found to be upregulated in lung fibrosis and cancer. Read More

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November 2018

Recent advances in the development of monoclonal antibodies for rabies post exposure prophylaxis: A review of the current status of the clinical development pipeline.

Vaccine 2018 Nov 29. Epub 2018 Nov 29.

The World Health Organization, Geneva, Switzerland.

Despite successful control in many parts of the world, rabies virus continues to result in tens of thousands of deaths each year. Death from rabies can be prevented by timely and appropriate post exposure prophylaxis including wound cleaning and administration of vaccine and rabies immunoglobulin. Currently, rabies immunoglobulin is derived from the blood plasma of horses or humans and has several limitations relating to supply, cost and quality. Read More

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November 2018

Role of phosphorylcholine in Streptococcus pneumoniae and nontypeable Haemophilus influenzae adherence to epithelial cells.

Auris Nasus Larynx 2018 Nov 29. Epub 2018 Nov 29.

Department of Otolaryngology, Head and Neck Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Objective: Phosphorylcholine (PC) is a structural component of Streptococcus pneumoniae (Spn) and nontypeable Haemophilus influenzae (NTHi), and is known to be associated with adherence through the platelet activating factor receptor (PAF-R). Furthermore, high PC expression is considered to be involved in Spn and NTHi virulence. In this study, we examined the influence of PC expression on the adherence of Spn and NTHi to epithelial cells in order to clarify the potential effectiveness of a vaccine targeting PC. Read More

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November 2018

Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells.

Cell 2018 Nov 13. Epub 2018 Nov 13.

Innate Pharma, 117 Avenue de Luminy, 13009 Marseille, France; Aix Marseille Université, INSERM, CNRS, Centre d'Immunologie de Marseille-Luminy, 13009 Marseille, France; Service d'Immunologie, Marseille Immunopole, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, 13005 Marseille, France. Electronic address:

Checkpoint inhibitors have revolutionized cancer treatment. However, only a minority of patients respond to these immunotherapies. Here, we report that blocking the inhibitory NKG2A receptor enhances tumor immunity by promoting both natural killer (NK) and CD8 T cell effector functions in mice and humans. Read More

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November 2018

Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome.

Clin Ther 2018 Nov 28. Epub 2018 Nov 28.

Section of Clinical Pharmacology, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Norway.

Purpose: Previous Phase II trials indicated clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in patients with myalgic encephalopathy/chronic fatigue syndrome (ME/CFS). The association between rituximab serum concentrations and the effect and clinical relevance of antidrug antibodies (ADAs) against rituximab in ME/CFS is unknown. We retrospectively measured rituximab concentrations and ADAs in serum samples from patients included in an open-label Phase II trial with maintenance rituximab treatment (KTS-2-2010) to investigate possible associations with clinical improvement and clinical and biochemical data. Read More

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November 2018

Edetate Disodium (EDTA) as a Polysorbate Degradation and Monoclonal Antibody Oxidation Stabilizer.

J Pharm Sci 2018 Nov 28. Epub 2018 Nov 28.

Pharmaceutical Research and Development, Pfizer Biotherapeutics Pharmaceutical Sciences, Chesterfield, Missouri 63017.

Polysorbates are frequently utilized in biotherapeutic formulations. Interest in assessing their stability, in particular the impact of their degradation products, on the stability of therapeutic proteins has been steadily growing in the past decade. The work presented summarizes a case study of a monoclonal antibody formulation that demonstrated a simultaneous loss of polysorbate and an increase in methionine oxidation. Read More

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November 2018