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https://www.readbyqxmd.com/read/28340323/a-key-to-the-backdoor-into-the-castle-the-clinical-ramifications-of-immunoediting-driven-by-antigenic-competition
#1
M G Hanna, Jason David Howard
Over the last decade the field of cancer biology has gained considerable data on genomic heterogeneity. This situation creates challenges and possibly opportunities for cancer treatment. The evolution of the tumor at all stages also requires the growing malignancy to confront and avoid the immune system. What we describe here is the interaction of two immune phenomena that work together to change the characteristics of the tumor, i.e., antigenic competition and immune editing. These two systems are mutually functional and their interaction is capable of altering the characteristics of the tumor for protection and survival in an immune competent host as well as restricting the diversity of the tumor clones...
March 24, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28339780/adverse-kidney-effects-of-epidermal-growth-factor-receptor-inhibitors
#2
Hassan Izzedine, Mark A Perazella
The epidermal growth factor receptor (EGFR) is implicated in various malignancies. The past decade has seen the development and widespread use of EGFR inhibitors for the successful treatment of such cancers. Available EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies. Class-related renal adverse events result in dual toxicity including tubular/electrolyte disorders and glomerulopathies. Tubular injury is common and mainly due to monoclonal antibodies while glomerulopathy is rare and related to various anti-EGFR agents...
February 23, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28333127/selective-intracellular-vaporisation-of-antibody-conjugated-phase-change-nano-droplets-in-vitro
#3
A Ishijima, K Minamihata, S Yamaguchi, S Yamahira, R Ichikawa, E Kobayashi, M Iijima, Y Shibasaki, T Azuma, T Nagamune, I Sakuma
While chemotherapy is a major mode of cancer therapeutics, its efficacy is limited by systemic toxicities and drug resistance. Recent advances in nanomedicine provide the opportunity to reduce systemic toxicities. However, drug resistance remains a major challenge in cancer treatment research. Here we developed a nanomedicine composed of a phase-change nano-droplet (PCND) and an anti-cancer antibody (9E5), proposing the concept of ultrasound cancer therapy with intracellular vaporisation. PCND is a liquid perfluorocarbon nanoparticle with a liquid-gas phase that is transformable upon exposure to ultrasound...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332312/antitumor-activity-of-chlpmab-2-a-human-mouse-chimeric-cancer-specific-antihuman-podoplanin-antibody-via-antibody-dependent-cellular-cytotoxicity
#4
Mika K Kaneko, Shinji Yamada, Takuro Nakamura, Shinji Abe, Yasuhiko Nishioka, Akiko Kunita, Masashi Fukayama, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology...
March 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28331448/antibody-mediated-rejection-a-review
#5
Jorge Carlos Garces, Sixto Giusti, Catherine Staffeld-Coit, Humberto Bohorquez, Ari J Cohen, George E Loss
BACKGROUND: Chronic antibody injury is a serious threat to allograft outcomes and is therefore the center of active research. In the continuum of allograft rejection, the development of antibodies plays a critical role. In recent years, an increased recognition of molecular and histologic changes has provided a better understanding of antibody-mediated rejection (AMR), as well as potential therapeutic interventions. However, several pathways are still unknown, which accounts for the lack of efficacy of some of the currently available agents that are used to treat rejection...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28331294/spotlight-on-blisibimod-and-its-potential-in-the-treatment-of-systemic-lupus-erythematosus-evidence-to-date
#6
REVIEW
Aleksander Lenert, Timothy B Niewold, Petar Lenert
B cells in general and BAFF (B cell activating factor of the tumor necrosis factor [TNF] family) in particular have been primary targets of recent clinical trials in systemic lupus erythematosus (SLE). In 2011, belimumab, a monoclonal antibody against BAFF, became the first biologic agent approved for the treatment of SLE. Follow-up studies have shown excellent long-term safety and tolerability of belimumab. In this review, we critically analyze blisibimod, a novel BAFF-neutralizing agent. In contrast to belimumab that only blocks soluble BAFF trimer but not soluble 60-mer or membrane BAFF, blisibimod blocks with high affinity all three forms of BAFF...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#7
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28329405/a-review-of-guselkumab-an-il-23-inhibitor-for-moderate-to-severe-plaque-psoriasis
#8
Z Nawas, M Hatch, E Ramos, M Liu, Y Tong, A Peranteau, S Tyring
Psoriasis is a chronic inflammatory skin disorder that affects 2% of the population. Evidence suggests that interleukin (IL)-23 plays a pivotal role in the pathogenesis of psoriasis. Guselkumab is a subcutaneously administered, humanized anti-IL23 monoclonal antibody indicated for the treatment of moderate-to-severe plaque psoriasis. Data from Phase I-III trials in this patient population reveal that guselkumab has proven to be superior to placebo or adalimumab based on achieving a Psoriasis Area and Severity Index (PASI) 90% reduction, or a static Physician Global Assessment (sPGA) score of 0 or 1 from baseline...
March 2017: Skin Therapy Letter
https://www.readbyqxmd.com/read/28329114/pcsk9-monoclonal-antibodies-reverse-the-pro-inflammatory-profile-of-monocytes-in-familial-hypercholesterolaemia
#9
Sophie J Bernelot Moens, Annette E Neele, Jeffrey Kroon, Fleur M van der Valk, Jan Van den Bossche, Marten A Hoeksema, Renate M Hoogeveen, Johan G Schnitzler, Marie T Baccara-Dinet, Garen Manvelian, Menno P J de Winther, Erik S G Stroes
Aims: Migration of monocytes into the arterial wall contributes to arterial inflammation and atherosclerosis progression. Since elevated low-density lipoprotein cholesterol (LDL-C) levels have been associated with activation of plasma monocytes, intensive LDL-C lowering may reverse these pro-inflammatory changes. Using proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) which selectively reduce LDL-C, we studied the impact of LDL-C lowering on monocyte phenotype and function in patients with familial hypercholesterolaemia (FH) not using statins due to statin-associated muscle symptoms...
February 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28328624/long-term-maintenance-of-clinical-endoscopic-and-radiographic-response-to-ustekinumab-in-moderate-to-severe-crohn-s-disease-real-world-experience-from-a-multicenter-cohort-study
#10
Christopher Ma, Richard N Fedorak, Gilaad G Kaplan, Levinus A Dieleman, Shane M Devlin, Nathan Stern, Karen I Kroeker, Cynthia H Seow, Yvette Leung, Kerri L Novak, Brendan P Halloran, Vivian W Huang, Karen Wong, Philip K Blustein, Subrata Ghosh, Remo Panaccione
BACKGROUND: Ustekinumab is a monoclonal antibody targeting interleukins 12 and 23. While effective in clinical trials for Crohn's disease (CD), long-term maintenance of response in the real-world setting is unclear. We aim to assess the efficacy of ustekinumab for maintaining clinical, endoscopic, and radiographic response in CD. METHODS: A retrospective multicenter cohort study was performed on patients with CD achieving steroid-free clinical response to ustekinumab induction, and advanced onto a regularly scheduled maintenance ustekinumab regimen between 2011 and 2016...
March 21, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28328317/antiproliferative-and-apoptotic-effects-of-novel-anti-ror1-single-chain-antibodies-in-hematological-malignancies
#11
Leili Aghebati-Maleki, Vahid Younesi, Behzad Baradaran, Jalal Abdolalizadeh, Morteza Motallebnezhad, Hamid Nickho, Dariush Shanehbandi, Jafar Majidi, Mehdi Yousefi
Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28326566/systematic-review-with-meta-analysis-comparative-efficacy-of-biologics-for-induction-and-maintenance-of-mucosal-healing-in-crohn-s-disease-and-ulcerative-colitis-controlled-trials
#12
REVIEW
A Cholapranee, G S Hazlewood, G G Kaplan, L Peyrin-Biroulet, A N Ananthakrishnan
BACKGROUND: Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome. AIM: To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC...
March 22, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28326356/effect-of-four-monthly-doses-of-a-human-monoclonal-anti-fgf23-antibody-krn23-on-quality-of-life-in-x-linked-hypophosphatemia
#13
Mary D Ruppe, Xiaoping Zhang, Erik A Imel, Thomas J Weber, Mark A Klausner, Takahiro Ito, Maria Vergeire, Jeffrey S Humphrey, Francis H Glorieux, Anthony A Portale, Karl Insogna, Munro Peacock, Thomas O Carpenter
X-linked hypophosphatemia (XLH) is characterized by lower extremity deformities that lead to bone and/or joint pain that result from decreased renal tubular reabsorption leading to hypophosphatemia caused by elevated levels of fibroblast growth factor 23 (FGF23). OBJECTIVE: Validate the use of SF-36v2 Health Survey (SF-36v2) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) to measure previously unstudied health-related quality of life (HRQoL) in XLH patients and determine the change in HRQoL before and after treatment with KRN23, a human monoclonal anti-FGF23 antibody...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28325256/how-have-evolutions-in-strategies-for-the-treatment-of-relapsed-refractory-multiple-myeloma-translated-into-improved-outcomes-for-patients
#14
REVIEW
Pieter Sonneveld, Edwin De Wit, Philippe Moreau
Although multiple myeloma (MM) remains incurable, the introduction of novel agents has improved clinical outcomes dramatically over the past 15 years. Response rates have risen from ∼30% with single agents to up to 90% with combination therapies. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, form the foundations for treatment of relapsed and/or refractory MM (RRMM). Newer agents, such as the IMiD pomalidomide, the histone deacetylase inhibitor panobinostat and the proteasome inhibitors carfilzomib and ixazomib, as well as the monoclonal antibodies daratumumab and elotuzumab, have further improved overall response rates in these patients...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28325214/antibody-based-cancer-therapy-successful-agents-and-novel-approaches
#15
D Hendriks, G Choi, M de Bruyn, V R Wiersma, E Bremer
Since their discovery, antibodies have been viewed as ideal candidates or "magic bullets" for use in targeted therapy in the fields of cancer, autoimmunity, and chronic inflammatory disorders. A wave of antibody-dedicated research followed, which resulted in the clinical approval of a first generation of monoclonal antibodies for cancer therapy such as rituximab (1997) and cetuximab (2004), and infliximab (2002) for the treatment of autoimmune diseases. More recently, the development of antibodies that prevent checkpoint-mediated inhibition of T cell responses invigorated the field of cancer immunotherapy...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28324270/obinutuzumab-a-review-in-rituximab-refractory-or-relapsed-follicular-lymphoma
#16
REVIEW
Sohita Dhillon
Obinutuzumab (Gazyva(®), Gazyvaro(®)) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the primary analysis of the large, phase III GADOLIN study, induction therapy with obinutuzumab plus bendamustine followed by obinutuzumab maintenance prolonged progression-free survival (PFS) to a statistically significant extent relative to induction with bendamustine monotherapy in patients with indolent non-Hodgkin's lymphoma (iNHL)...
March 21, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28323504/pembrolizumab-use-for-the-treatment-of-advanced-melanoma
#17
Pol Specenier
Until recently, overall long term survival in patients with stage IV melanoma was lower than 10 %. However, the treatment of melanoma has evolved rapidly over the last few years, with the advent of inhibitors of BRAF and MEK and of immunotherapeutic agents including ipilimumab, nivolumab, and pembrolizumab. Areas covered: This is a comprehensive review of the literature on the role of pembrolizumab in melanoma. Pembrolizumab is a Programmed Death Receptor 1 (PD-1) directed monoclonal antibody which is approved by FDA and EMA for the treatment of patients with metastatic melanoma...
March 21, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28323224/progressive-multifocal-leukoencephalopathy-and-rheumatoid-arthritis-treatments
#18
Gaëlle Clavel, Antoine Moulignier, Luca Semerano
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system due to reactivation of the JC virus (JCV). PML is extremely uncommon despite the high prevalence of the virus in the general population. No specific treatment is available, and the prognosis is bleak. The diagnosis is based on brain imaging findings, detection of the JCV genome in cerebrospinal fluid samples and, in some cases, histological studies of the brain lesions. The pathophysiological mechanisms that drive the development of PML are incompletely understood...
March 16, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28323034/co-targeting-of-egfr-and-autophagy-signaling-is-an-emerging-treatment-strategy-in-metastatic-colorectal-cancer
#19
Evangelos Koustas, Michalis V Karamouzis, Chrysovalantou Mihailidou, Dimitrios Schizas, Athanasios G Papavassiliou
The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic Colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR moAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28322834/anti-human-cd14-monoclonal-antibody-improves-survival-following-sepsis-induced-by-endotoxin-but-not-following-polymicrobial-infection
#20
Masaki Nakamura, Takashi Takeuchi, Kamon Shirakawa, Shoji Furusako
Cluster of differentiation 14 (CD14), a pattern recognition receptor expressed on myeloid cells and a critical component of the innate immune system, mediates local and systemic host responses to gram-negative bacterial products, including lipopolysaccharide (LPS). Therefore, CD14 is an attractive target for development of sepsis therapies, and several monoclonal anti-CD14 antibodies have been reported. In this study, we prepared an anti-human CD14 monoclonal antibody, F1024-1-3, which suppressed LPS-induced upregulation of pro-inflammatory cytokines and an adhesion molecule in human peripheral mononuclear cells and human vascular endothelial cells...
March 16, 2017: European Journal of Pharmacology
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