Antigen-expressing immunostimulatory liposomes as a genetically programmable synthetic vaccine

Liposomes are versatile (sub)micron-sized membrane vesicles that can be used for a variety of applications, including drug delivery and in vivo imaging but they also represent excellent models for artificial membranes or cells. Several studies have demonstrated that in vitro transcription and translation can take place inside liposomes to obtain compartmentalized production of functional proteins within the liposomes (Kita et al. in Chembiochem 9(15):2403–2410, 2008; Moritani et al.in FEBS J, 2010; Kuruma et al. in Methods Mol Biol 607:161–171, 2010; Murtas et al. in Biochem Biophys Res Commun 363(1):12–17, 2007; Sunami et al. in Anal Biochem 357(1):128–136, 2006; Ishikawa et al. in FEBS Lett 576(3):387–390, 2004; Oberholzer et al. in Biochem Biophys Res Commun 261(2):238–241, 1999). Such a minimal artificial cell-based model is ideal for synthetic biology based applications. In this study, we propose the use of liposomes as artificial microbes for vaccination. These artificial microbes can be genetically programmed to produce specific antigens at will. To show proof-of-concept for this artificial cell-based platform, a bacterial in vitro transcription and translation system together with a gene construct encoding the model antigen β-galactosidase were entrapped inside multilamellar liposomes. Vaccination studies in mice showed that such antigen-expressing immunostimulatory liposomes (AnExILs) elicited higher specific humoral immune responses against the produced antigen (β-galactosidase) than control vaccines (i.e. AnExILs without genetic input, liposomal β-galactosidase or pDNA encoding β-galactosidase). In conclusion, AnExILs present a new platform for DNA-based vaccines which combines antigen production, adjuvanticity and delivery in one system and which offer several advantages over existing vaccine formulations

Personalised dosing: Printing a dose of one's own medicine

© 2015 Elsevier B.V. All rights reserved. Ink-jet printing is a versatile, precise and relatively inexpensive method of depositing small volumes of solutions with remarkable accuracy and repeatability. Although developed primarily as a technology for image reproduction, its areas of application have expanded significantly in recent years. It is particularly suited to the manufacture of low dose medicines or to short production runs and so offers a potential manufacturing solution for the paradigm of personalised medicines. This review discusses the technical and clinical aspects of ink-jet printing that must be considered in order for the technology to become widely adopted in the pharmaceutical arena and considers applications in the literature

Modest decline in late mortality following Hodgkin's disease in the southeastern Netherlands since 1972

Since prolonged remission can be induced in the majority of patients with Hodgkin's disease (HD), treatment-related mortality and morbidity have emerged, We investigated whether awareness of toxicity diminished treatment-related mortality for unselected patients treated between 1972 and 1993 in general hospitals in the southeastern Netherlands. We also estimated the prevalence of treatment-related morbidity among patients treated in the 1980s. Data were collected on all 345 HD patients registered in the Eindhoven Cancer Registry between 1972 and 1993, Medical records and histology were reviewed; follow-up ended in 1994, Administration of MOPP chemotherapy decreased, and there was a shift from total nodal irradiation to less extended low-dose radiotherapy. For cured patients the 10-year relative survival improved from 84% in the 1970s to 90% in the 1980s, which is reflected by a decline in excess mortality from 16% to 10%. The 10-year relative mortality risk due to secondary malignancies decreased from 4.3 (95% CI, 1.2-7.4) to 3.0 (CI 0.2-5.8), which is also reflected by a decline in the 10-year cumulative incidence for all cancers from 10% to 5%, However, the relative risk of late cardiovascular death, which is closely related to previous irradiation, barely changed, as shown by a decrease from 2.4 (CI0.4-4.5) to 2.2 (CI.0-4.7). HD survivors profited less from the sharp decline in cardiovascular mortality observed for the general population. Among patients, the prevalence of serious treatment-related morbidity 5 years or more after initial diagnosis was 34%, In conclusion, modest decline in excess mortality among cured HD patients was observed in the 1980s, as reflected by a decrease in mortality due to second malignancies. However, late mortality, especially due to radiation-related cardiovascular disease, is still substantial. About one third of HD survivors suffer radiation-induced sequelae, Clinical trials to find ways to minimize iatrogenic complications are important

Adjuvant postoperative radiotherapy for adenocarcinoma of the rectum and rectosigmoid

Results are presented of a retrospective study on 178 patients receiving adjuvant postoperative radiotherapy after curative surgery for adenocarcinoma of the rectum and rectosigmoid. Tumorstages according to Gunderson-Sosin were B2: 67, B3: 5, C1: 9, C2: 94, and C3: 3. Median total dosage was 50 Gy (range: 10-66 Gy), with a median dose per fraction of 2.0 Gy, 5 fractions per week. The censored overall 5-year survival rate was 42%, and 5-year disease-free survival rate was 37%. The respective rates for stage B2 patients (n = 67) were 59% and 53%, and for stage C2 patients (n = 94), 25% and 25%. Recurrences occurred in 89% within 3 years, 8% in the fourth, and 1% in the fifth year of follow-up. Five-year local relapse rates were 27% for the stage B2 tumors and 40% for the stage C2 tumors. For survival, stage (P =.006), grade (P =.02), fixation at surgery (P =.03), and gender (P =.03) were independent prognostic factors. With local relapse-free probability (LRFP) as endpoint, grade (P <.02) was an independent prognostic factor. Dose of radiation was not of prognostic significance, neither for survival (P =.63) nor for LRFP (P =.61). Since improvement should be made in locoregional control, initiatives are taken to start preoperative radiotherapy; furthermore, the key role of surgery is emphasized

Modest decline in late mortality following Hodgkin's disease in the southeastern Netherlands since 1972

Since prolonged remission can be induced in the majority of patients with Hodgkin's disease (HD), treatment-related mortality and morbidity have emerged, We investigated whether awareness of toxicity diminished treatment-related mortality for unselected patients treated between 1972 and 1993 in general hospitals in the southeastern Netherlands. We also estimated the prevalence of treatment-related morbidity among patients treated in the 1980s. Data were collected on all 345 HD patients registered in the Eindhoven Cancer Registry between 1972 and 1993, Medical records and histology were reviewed; follow-up ended in 1994, Administration of MOPP chemotherapy decreased, and there was a shift from total nodal irradiation to less extended low-dose radiotherapy. For cured patients the 10-year relative survival improved from 84% in the 1970s to 90% in the 1980s, which is reflected by a decline in excess mortality from 16% to 10%. The 10-year relative mortality risk due to secondary malignancies decreased from 4.3 (95% CI, 1.2-7.4) to 3.0 (CI 0.2-5.8), which is also reflected by a decline in the 10-year cumulative incidence for all cancers from 10% to 5%, However, the relative risk of late cardiovascular death, which is closely related to previous irradiation, barely changed, as shown by a decrease from 2.4 (CI0.4-4.5) to 2.2 (CI.0-4.7). HD survivors profited less from the sharp decline in cardiovascular mortality observed for the general population. Among patients, the prevalence of serious treatment-related morbidity 5 years or more after initial diagnosis was 34%, In conclusion, modest decline in excess mortality among cured HD patients was observed in the 1980s, as reflected by a decrease in mortality due to second malignancies. However, late mortality, especially due to radiation-related cardiovascular disease, is still substantial. About one third of HD survivors suffer radiation-induced sequelae, Clinical trials to find ways to minimize iatrogenic complications are important