Yeng-Tseng Wang, Lea-Yea Chuang
Antibody drugs are very useful tools for the treatment of many chronic diseases. Recently, however, patients and doctors have encountered the problem of drug resistance. How to improve the affinity of antibody drugs has therefore become a pressing issue. Ibalizumab is a humanized monoclonal antibody that binds human CD4, the primary receptor for human immunodeficiency virus type 1. This study investigates the mutation residues of the complementarity determining regions of Ibalizumab. We propose using the wild and mutations of Ibalizumab-human CD4 receptor complex structures, molecular dynamics techniques, alanine-scanning mutagenesis calculations and solvated interaction energies methods to predict the binding free energy of the Ibalizumab-human CD4 receptor complex structures...
January 2015: Journal of Computer-aided Molecular Design
Bernard S Kaplan, Rebecca L Ruebner, Joann M Spinale, Lawrence Copelovitch
Tremendous advances have been made in understanding the pathogenesis of atypical Hemolytic Uremic Syndrome (aHUS), an extremely rare disease. Insights into the molecular biology of aHUS resulted in rapid advances in treatment with eculizumab (Soliris(®), Alexion Pharmaceuticals Inc.). Historically, aHUS was associated with very high rates of mortality and morbidity. Prior therapies included plasma therapy and/or liver transplantation. Although often life saving, these were imperfect and had many complications...
May 2014: Intractable & Rare Diseases Research
Nathalie Esser, Nicolas Paquot, André J Scheen
INTRODUCTION: There is a growing body of evidence to suggest that chronic silent inflammation is a key feature in abdominal obesity, metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease (CVD). These observations suggest that pharmacological strategies, which reduce inflammation, may be therapeutically useful in treating obesity, type 2 diabetes and associated CVD. AREA COVERED: The article covers novel strategies, using either small molecules or monoclonal antibodies...
March 2015: Expert Opinion on Investigational Drugs
Jamese J Hilliard, Vivekananda Datta, Christine Tkaczyk, Melissa Hamilton, Agnieszka Sadowska, Omari Jones-Nelson, Terrence O'Day, William J Weiss, Szabolcs Szarka, Vien Nguyen, Laszlo Prokai, JoAnn Suzich, C Kendall Stover, Bret R Sellman
Alpha-toxin (AT) is a major virulence determinant in Staphylococcus aureus skin and soft tissue infection models. We previously demonstrated that prophylactic administration of 2A3, an AT-neutralizing monoclonal antibody (MAb), prevents S. aureus disease in a mouse dermonecrosis model by neutralizing AT-mediated tissue necrosis and immune evasion. In the present study, MEDI4893*, an affinity-optimized version of 2A3, was characterized for therapeutic activity in the dermonecrosis model as a single agent and in combination with two frontline antibiotics, vancomycin and linezolid...
January 2015: Antimicrobial Agents and Chemotherapy
Maria Kanariou, Sofia Tantou, Ioanna Varela, Maria Raptaki, Chrissa Petropoulou, Ioannis Nikas, Manthoula Valari
Neonatal onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic cutaneous and articular (CINCA) syndrome is a rare, early-onset autoinflammatory disorder and the most severe form of cryopyrin-associated periodic syndrome, which is associated with overproduction of interleukin (IL)-1β. This is a case report of a 70-day-old boy, who was diagnosed with NOMID/CINCA syndrome and who has been treated with anti-IL-1β monoclonal antibody (canakinumab) since then, despite his early infancy. The patient presented with fever, aseptic meningitis, and rash...
November 2014: Pediatrics
Mónica Enguita-Germán, Puri Fortes
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Only 30%-40% of the patients with HCC are eligible for curative treatments, which include surgical resection as the first option, liver transplantation and percutaneous ablation. Unfortunately, there is a high frequency of tumor recurrence after surgical resection and most HCC seem resistant to conventional chemotherapy and radiotherapy. Sorafenib, a multi-tyrosine kinase inhibitor, is the only chemotherapeutic option for patients with advanced hepatocellular carcinoma...
October 27, 2014: World Journal of Hepatology
Karen A Kirby, Yee Tsuey Ong, Atsuko Hachiya, Thomas G Laughlin, Leslie A Chiang, Yun Pan, Jennifer L Moran, Bruno Marchand, Kamalendra Singh, Fabio Gallazzi, Thomas P Quinn, Kazuhisa Yoshimura, Toshio Murakami, Shuzo Matsushita, Stefan G Sarafianos
Humanized monoclonal antibody KD-247 targets the Gly(312)-Pro(313)-Gly(314)-Arg(315) arch of the third hypervariable (V3) loop of the HIV-1 surface glycoprotein. It potently neutralizes many HIV-1 clade B isolates, but not of other clades. To understand the molecular basis of this specificity, we solved a high-resolution (1.55 Å) crystal structure of the KD-247 antigen binding fragment and examined the potential interactions with various V3 loop targets. Unlike most antibodies, KD-247 appears to interact with its target primarily through light chain residues...
January 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Vicki A Morrison
The introduction of novel agents to the therapeutic armamentarium for oncologic, rheumatologic, and neurologic disorders has resulted in major clinical advances. These agents impact immune function, resulting in a discrete spectrum of infectious complications. Purine analogues and alemtuzumab alter cell-mediated immunity, resulting in opportunistic viral/fungal infections. Herpes zoster incidence increases with bortezomib. Hepatitis B reactivation may occur with rituximab. Cases of progressive multifocal leukoencephalopathy have occurred following monoclonal antibody therapy...
November 15, 2014: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Mamitaro Ohtsuki, Akimichi Morita, Masatoshi Abe, Hidetoshi Takahashi, Noriko Seko, Alexander Karpov, Tomohiro Shima, Charis Papavassilis, Hidemi Nakagawa
Secukinumab, a fully human anti-IL-17A monoclonal antibody, neutralizes IL-17A, a key cytokine in the pathogenesis of psoriasis. Efficacy and safety of secukinumab was evaluated in Japanese patients with moderate-to-severe plaque psoriasis as part of a large Phase 3 global study (ERASURE). In this 52-week, double-blind study ( Identifier: NCT01365455, JapicCTI-111529), 87 patients from Japan (11.8% of 738 patients randomized in the overall study population) were equally randomized to receive secukinumab 300 mg or 150 mg, or placebo once weekly at baseline and at Weeks 1, 2, 3 and 4, then every 4 weeks...
December 2014: Journal of Dermatology
Samuel Sloan, Perry Maxwell, Manuel Salto-Tellez, Maurice B Loughrey
Crohn's disease is a chronic inflammatory bowel disease of unknown aetiology. Mucosal inflammatory dysregulation is likely important, with increased production of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNFα). The chimeric monoclonal antibody, infliximab, inhibits TNFα and promotes intestinal mucosal healing. Despite this, many patients still require surgical intervention. Patients who have undergone colonic resection post-infliximab therapy, show markedly variable morphological response to treatment...
December 2014: Pathology International
H Saeki, H Nakagawa, T Ishii, Y Morisaki, T Aoki, P-Y Berclaz, M Heffernan
BACKGROUND: Ixekizumab, an anti-IL-17A monoclonal antibody, demonstrated a high level of efficacy in moderate-to-severe plaque psoriasis (PP) patients. OBJECTIVE: To evaluate the efficacy and safety of open-label ixekizumab in Japanese patients with moderate-to-severe PP, erythrodermic psoriasis (EP) and generalized pustular psoriasis (GPP). METHODS: Patients received 160-mg subcutaneous ixekizumab injection at Week 0, 80-mg every 2 weeks through Week 12 and 80-mg every 4 weeks through Week 24...
June 2015: Journal of the European Academy of Dermatology and Venereology: JEADV
Tejas Suresh, Lisa X Lee, Jitesh Joshi, Stefan K Barta
The CD20-directed monoclonal antibody rituximab established a new era in lymphoma therapy. Since then other epitopes on the lymphoma surface have been identified as potential targets for monoclonal antibodies (mAb). While most mAbs eliminate lymphoma cells mainly by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity or direct cell death, others counter mechanisms utilized by malignant cells to evade immune surveillance. Expression of PD-L1 on malignant or stromal cells in the tumor environment for example leads to T-cell anergy...
September 9, 2014: Journal of Hematology & Oncology
Clement Chung, Rosetta Lee
Chronic lymphocytic leukemia (CLL) is a neoplasm resulting from the progressive accumulation of functionally incompetent monoclonal B lymphocytes in the blood, bone marrow, lymph nodes, and spleen. It is the most common leukemia in Western countries and typically occurs in elderly patients. Initial treatment of CLL often includes a first-generation anti-CD20 antibody (rituximab) with chemotherapy and is the current standard of treatment for "younger" old adults (< 70 yrs of age) or older, clinically fit patients...
December 2014: Pharmacotherapy
Tiehong Zhang, Hongchang Shen, Wei Dong, Xiao Qu, Qi Liu, Jiajun Du
The insulin-like growth factor type 1 receptor (IGF-1R) plays an essential role in the development of numerous cancers. Figitumumab (CP) is not only a monoclonal antibody, it also has agonist activity on IGF-1R. The antitumor activity of CP in esophageal squamous cell carcinoma (ESCC) is still unclear. In our study, we identified IGF-1R as an independent prognostic factor in ESCC patients, and investigated the antitumor effects of CP in ESCC cell lines. CP suppressed tumor growth and sensitized cells to chemotherapeutic drugs...
October 31, 2014: Scientific Reports
William P Kennedy, J Abraham Simon, Carolyn Offutt, Priscilla Horn, Ann Herman, Michael J Townsend, Meina T Tang, Jane L Grogan, Frank Hsieh, John C Davis
INTRODUCTION: Tumor necrosis factor (TNF) and, possibly, lymphotoxin alpha (LTα) signaling contribute to inflammation and rheumatoid arthritis (RA) pathogenesis. Pateclizumab (anti-lymphotoxin- alpha; MLTA3698A) is a humanized monoclonal antibody that blocks and depletes anti-LTα. This phase 2, randomized, head-to-head, active- and placebo-controlled trial examined the safety and efficacy of pateclizumab compared to adalimumab in RA patients with an inadequate response to disease-modifying antirheumatic drugs (DMARD-IR)...
October 30, 2014: Arthritis Research & Therapy
Tim Raine
Two decades ago, the first reports of the use of monoclonal antibodies targeting tumour-necrosis factor α heralded a revolution in treatment options for moderate to severe Crohn's disease and ulcerative colitis. Nonetheless, patients with refractory disease or loss of treatment response are all too familiar to gastroenterologists. Preventing the infiltration of the gastrointestinal mucosa by circulating cells of the immune system using antibodies targeting the adhesion molecules involved represents an attractive new treatment option...
October 2014: United European Gastroenterology Journal
Anne Marie-Cardine, Nicolas Viaud, Nicolas Thonnart, Rachel Joly, Stéphanie Chanteux, Laurent Gauthier, Cécile Bonnafous, Benjamin Rossi, Mathieu Bléry, Carine Paturel, Armand Bensussan, Martine Bagot, Hélène Sicard
Advanced cutaneous T-cell lymphoma (CTCL) remains an unmet medical need, which lacks effective targeted therapies. In this study, we report the development of IPH4102, a humanized monoclonal antibody that targets the immune receptor KIR3DL2, which is widely expressed on CTCL cells but few normal immune cells. Potent antitumor properties of IPH4102 were documented in allogeneic human CTCL cells and a mouse model of KIR3DL2(+) disease. IPH4102 antitumor activity was mediated by antibody-dependent cell cytotoxicity and phagocytosis...
November 1, 2014: Cancer Research
Kei Higashikawa, Katsuharu Yagi, Keiko Watanabe, Shinichiro Kamino, Masashi Ueda, Makoto Hiromura, Shuichi Enomoto
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) targeted therapy by anti-CTLA-4 monoclonal antibody (mAb) is highly effective in cancer patients. However, it is extremely expensive and potentially produces autoimmune-related adverse effects. Therefore, the development of a method to evaluate CTLA-4 expression prior to CTLA-4-targeted therapy is expected to open doors to evidence-based and cost-efficient medical care and to avoid adverse effects brought about by ineffective therapy. In this study, we aimed to develop a molecular imaging probe for CTLA-4 visualization in tumor...
2014: PloS One
Gail M Wilkes
No abstract text is available yet for this article.
July 2011: Oncology (Williston Park, NY)
Wei-Xiang Qi, Shen Fu, Qing Zhang, Xiao-Mao Guo
BACKGROUND: Anti-epidermal growth factor receptor (EGFR)-monoclonal antibodies (MoAbs) have been widely used in a variety of malignancies. Severe infections (≥grade 3) are potentially life-threatening adverse events with these drugs. However, the contribution of anti-EGFR MoAbs to infections is still unknown. We performed this meta-analysis to determine the overall incidence and risk of severe infections in cancer patients treated with these drugs. METHODS: The databases of PubMed and abstracts presented at oncology conferences and published in the proceedings were searched for relevant studies from January 2000 to May 2014...
November 5, 2014: BMC Medicine
2014-11-11 14:34:49
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