Ultra-small superparamagnetic iron oxides for metastatic lymph node detection: back on the block.

In the past 15 years, encouraging clinical results for the detection of small lymph node metastases was obtained by the use of Combidex-enhanced MRI (CEM, also known as magnetic resonance lymphography). Withdrawal of the European Medicines Agency approval application by the manufacturer made it impossible for patients to benefit from this agent; a loss, especially for men with prostate cancer. Current conventional imaging techniques are not as accurate as CEM is, thus a surgical diagnostic exploration (extended lymph node dissection) is still the preferred technique to evaluate the lymph nodes, resulting in peri- and postoperative complications. In 2013, the Radboud University Medical Center (Radboudumc) obtained all licenses and documentation for the production process of Combidex (ferumoxtran-10), and manufactured the contrast agent under supervision of the Department of Pharmacy. Since 2014, 310 men with prostate cancer have been examined with CEM in the Radboudumc. Within this cohort, seven minor possibly contrast-related adverse effects were observed after administration of Combidex. As the contrast agent is now back again in the Netherlands, this review highlights the working mechanism, previous results, observed side effects since the reintroduction, and the future perspectives for Combidex. WIREs Nanomed Nanobiotechnol 2018, 10:e1471. doi: 10.1002/wnan.1471 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Intranasal administration of a proteosome-influenza vaccine is well-tolerated and induces serum and nasal secretion influenza antibodies in healthy human subjects.

Two randomized, blinded, active comparator-controlled trials of a prototype monovalent A/Beijing/262/95 (H1N1) - proteosome vaccine delivered by intranasal spray were performed in healthy adults. Overall, the intranasal proteosome-adjuvanted vaccine was well-tolerated with only mild stuffy nose and rhinorrhea seen more frequently in recipients of vaccine than in recipients of intranasal saline, and there were no serious adverse events. The intranasal proteosome-adjuvanted vaccine induced serum hemagglutination inhibiting (HAI) and nasal secretory IgA (sIgA) responses specific for the influenza antigen. Serum HAI responses were most influenced by the dosage level, whereas mucosal sIgA responses, although demonstrable with both single-dose and two-dose vaccine regimens, appeared to be greater in response to two-dose regimens (regardless of dose level). Further evaluation of mucosal influenza immunization using the proteosome adjuvant/delivery system is clearly warranted.

Safety and immunogenicity of 26-valent group a streptococcus vaccine in healthy adult volunteers.

BACKGROUND: Group A streptococcus (GAS) causes illness ranging from uncomplicated pharyngitis to life-threatening necrotizing fasciitis, toxic shock, and rheumatic fever. Attempts to develop an M protein-based vaccine have been hindered by the fact that some M proteins elicit both protective antibodies and antibodies that cross-react with human tissues. New molecular techniques have allowed the previous obstacles to be largely overcome. METHODS: The vaccine is comprised of 4 recombinant proteins adsorbed to aluminum hydroxide that contain N-terminal peptides from streptococcal protective antigen and M proteins of 26 common pharyngitis, invasive, and/or rheumatogenic serotypes. Thirty healthy adult subjects received intramuscular 26-valent GAS vaccine (400 microg) at 0, 1, and 4 months, with clinical and laboratory follow-up for safety and immunogenicity using assays for tissue cross-reactive antibodies, type-specific M antibodies to 27 vaccine antigens, and functional (opsonization) activity of M protein antibodies. RESULTS: The incidence of local reactogenicity was similar to that for other aluminum hydroxide-adsorbed vaccines in adults. No subject developed evidence of rheumatogenicity or nephritogenicity, and no induction of human tissue-reactive antibodies was detected. Overall, 26 of 27 antigenic peptides evoked a >4-fold increase in the geometric mean antibody titer over baseline. The mean log2 fold-increase in serum antibody titer (+/- standard error of the mean) for all 27 antigens was 3.67 +/- 0.21. A significant mean log2 reduction in streptococcal bacterial counts in serum samples obtained after immunization was seen in opsonization assays for all M serotypes. CONCLUSIONS: On the basis of epidemiological data demonstrating that the majority of cases of pharyngitis, necrotizing fasciitis, and other invasive streptococcal infections are caused by a limited number of serotypes, this 26-valent vaccine could have significant impact on the overall burden of streptococcal disease.