Ultrasonic atomization and subsequent desolvation for monoclonal antibody (mAb) to the glycoprotein (GP) IIIa receptor into drug eluting stent

An eluting-stent system with mAb dispersed in the PLLA (poly (L-lactic acid)) was validated in vitro. Specifically designed spray equipment based on the principle of ultrasonic atomization was used to produce a thin continuous PLLA (poly (L-lactic acid)) polymer coating incorporating monoclonal antibody (mAb). This PLLA coating was observed in light microscopy (LM) and scanning electron microscopy (SEM). The concentration of the monoclonal antibody (mAb) to the platelet glycoprotein (GP) IIIa receptor and the eluting rate were then measured by a radioisotope technique with ¹²⁵I-labelled GP IIIa mAb. An in vitro perfusion circuit was designed to evaluate the release rates at different velocities (10 or 20 ml min^?1). The PLLA coating was thin and transparent, uniformly distributed on the surface of the stent. Three factors influenced its thickness: PLLA concentration, duration and gas pressure. The concentration of mAb was influenced by the duration of absorption and the concentration of the mAb solution; the maximum was 1662.23 ± 38.83 ng. The eluting rate was fast for the first 2 h, then decreased slowly and attained 80% after 2 weeks. This ultrasonic atomization spray equipment and technological process to prepare protein eluting-stents were proved to be effective and reliable.     

玻璃体腔注射Ranibizumab联合25G+微创玻璃体视网膜术治疗严重PDR

目的:研究玻璃体腔注射ranibizumab辅助25G+微创玻璃体视网膜术(vitreous retinal surgery,VRS)治疗严重增生性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)的疗效及安全性.方法:选取我院2015-03/2016-06确诊为严重PDR患者61例74眼,根据自愿原则,31例37眼在VRS前行玻璃体腔注射ranibizumab治疗,设为联合组,30例37眼行纯VRS,设为对照组.对比两组术后的玻璃体积血率、BCVA(LogMAR)、平均眼压、黄斑中心凹视网膜厚度及并发症.结果:联合组术后1wk玻璃体积血率为8%,显著低于对照组的27%,差异有统计学意义(x2=4.573,P=0.032);联合组术后>1~4wk玻璃体积血率为0,而对照组为16%,差异有统计学意义(P=0.033);联合组术后>1~3mo玻璃体积血率为0,低于对照组的8%,差异无统计学意义(P=0.238);术后3mo联合组的BCVA明显好于对照组,差异有统计学意义(t=2.320,P=0.023);术后3mo两组平均眼压差异无统计学意义(t=0.516,P=0.608);术后3mo联合组平均黄斑中心凹视网膜厚度为298.8±78.3μm,显著低于对照组的357.1±86.2μm,差异有统计学意义(t=3.045,P=0.003);联合组一过性高眼压率为14%,显著低于对照组的32%,差异有统计学(x2=10.385,P=0.001);联合组的视网膜前膜率、复发性牵拉性视网膜脱落率及新生血管性青光眼率均低于对照组,但差异无统计学意义(P>0.05).结论:玻璃体腔注射ranibizumab辅助VRS虽存在一定争议,但在合适的剂量、频率和时间下能取得显著的疗效,安全性也较高.     

Small molecules for small minds? The case for biologic pharmaceuticals

Biologic pharmaceuticals are gaining in both market share and clinical utility compared with small molecule therapeutics. This market growth is, in part, reflective of a field of science entering its toddlerhood, where with increased maturity, both development timelines and costs of manufacturing for these complex molecules will decrease, further enhancing the profitability side of the equation. Although a firm understanding of the rules governing toxicity (especially antibody responses to therapeutic proteins) remains to be defined, it is clear that proteins are less prone to much of the idiosyncratic toxicity associated with small molecule drug candidates. Proteins are disadvantaged in that they are unlikely to find much use in targeting intercellular processes; however, they have clear strengths over small molecules in targeting protein–protein interactions and the specific targeting of surface features of particular cells (e.g., in oncology). As each aspect of protein pharmaceutical technology advances, it is clear that this will be the major area for growth in the industry over the next decade.     

Monoclonal antibodies currently in Phase II and III trials for multiple myeloma

Introduction: Despite the introduction of novel agents, such as thalidomide, lenalidomide and bortezomib, multiple myeloma (MM) remains an incurable disease and new therapies are needed. mAbs are a new promising anticancer treatment option.

Areas covered: This review will focus on mAbs that are currently under evaluation in Phase II and III clinical trials, as single agent and in combination with established treatment options.

Expert opinion: mAbs are a new strategy against MM, and they have demonstrated encouraging results in preclinical models. mAbs have a relatively benign side-effect profile and work synergistically with traditional chemotherapies and with immunomodulatory drugs and proteasome inhibitors.     

A review of tositumomab and I131 tositumomab radioimmunotherapy for the treatment of follicular lymphoma

The CD20 antigen has become a major therapeutic target in the management of follicular and other Bcell non-Hodgkin’s lymphomas. The murine monoclonal antibody, tositumomab, on binding CD20, is able to induce antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and apoptosis. In addition, when radioiodinated, the antibody exploits the tumour’s sensitivity to ionising radiation by direct targeting of the malignant cell. Tositumomab and Iodine (I¹³¹) tositumomab (Bexxar^®, GlaxoSmithKline, Philadelphia, PA, USA) is administered in two steps. The dosimetric step determines individual patient pharmacokinetics, allowing a patient- specific dose to be calculated. This is followed by the therapeutic step, with administration of the therapeutic dose between 7 and 14 days after the dosimetric dose. Over a decade’s worth of experience in clinical trials has determined the efficacy and safety of the regimen in a variety of clinical ci-rcumstances; establishment of exactly where the regimen fits amongst the algorithm for the management of follicular lymphoma continues.     

Current situation of zalutumumab

Background: Increased EGFR expression has been observed in many tumours. This overexpression usually correlates with a more advanced disease stage, a poorer prognosis and a worse chemotherapy response. EGFR inhibition has been considered an attractive approach in cancer treatment. Various strategies to intervene in EGFR signalling have been developed, mainly receptor inhibition of extracellular domain using anti-EGFR monoclonal antibodies and receptor inhibition on the intracytoplasmic domain using small-molecule tyrosine kinase inhibitors. Cetuximab and panitumumab are the most developed anti-EGFR monoclonal antibodies, and there is plenty of published information about their current status Objective/methods: In this review we focus on Zalutumumab, an IgG1 completely human anti-EGFR monoclonal antibody. Results/conclusions: Apart from EGFR inhibition, another anti-neoplastic effect of zalutumumab has also been postulated, mediated by immune mechanisms, specifically by antibody-dependent cell cytotoxicity. Zalutumumab is under clinical development, mainly for squamous cell cancer of head and neck and there are also ongoing trials in NSCLC and colorectal cancer.     

Update on reslizumab for eosinophilic asthma

The cellular uptake of oligomeric nucleic acid-based tools and drugs including small-interfering RNA (siRNA) represents a major technical hurdle for the biologic effectiveness and therapeutic success in vivo. Subsequent to cellular delivery it is crucial to direct siRNA to the cellular location where it enters the RNA interference pathway. Here the authors summarise evidence that functionally active siRNA represents a minor fraction in the order of 1% of total siRNA inside a given target cell. Exploiting possibilities of steering intracellular release or trafficking of siRNA bears the potential of substantially increasing the biological activity of siRNA. The recently described phosphorothioate stimulated cellular delivery of siRNA makes use of the caveolar system ending in the Golgi apparatus, which contrasts all other known delivery systems. Therefore, it represents an attractive alternative to study whether promoted intracellular release is related to increased target suppression and, thus, increased phenotypic biologic effectiveness.     

Disabling inflammatory pathways with biologics and resulting clinical outcomes in severe asthma

Introduction: Patients with severe asthma have a significant unmet need with persistent symptoms and/or frequent exacerbations despite high intensity treatment. These severe unrelenting symptoms have a huge impact on heathcare resources due to frequent hospital admissions and requirement for intensive and expensive medications. There is a compelling need for more effective and safer therapies to help severe asthma sufferers to achieve adequate control of their disease.

Areas covered: Expanding knowledge of innate and adaptive immune responses has led to development of new biologic approaches for severe asthma. Here, the authors will review the existing efficacy and safety data from clinical trials of some of the new biologic therapies that are in development for severe asthma. Their specific role in distinctively targeted subpopulations of severe asthmatics will be also discussed.

Expert opinion: Defining and phenotyping severe asthma patients will become increasingly important as some patients who were previously classified as having severe asthma may become well-controlled with a targeted phenotype-specific treatment. However, pharmacoeconomic concerns should also be taken into account given the elevated acquisition costs of recombinant human monoclonals and of the diagnostic screening procedures for the identification of potential responders.     

Bacterial meningitis: new therapeutic approaches

Bacterial meningitis remains a disease with high mortality and long-term morbidity. Outcome critically depends on the rapid initiation of effective antibiotic therapy. Since a further increase of the incidence of pathogens resistant to antibacterials can be expected both in community-acquired and nosocomial bacterial meningitis, the choice of an optimum initial empirical antibiotic regimen will gain significance. In this context, the use of antibiotics which are bactericidal but do not lyse bacteria, may emerge as a therapeutic option. Conversely, the role of corticosteroids, which decrease the entry of hydrophilic antibacterials into the cerebrospinal fluid, as adjunctive therapy will probably decline as a consequence of the increasing antibiotic resistance of bacteria causing meningitis. Consequent vaccination of all children at present is the most efficient manner to reduce disease burden.