| 1. |
- Bartholeyns, J, et al.
(författare)
-
Cellular vaccines
- 1998
-
Ingår i: Research in Immunology. - 0923-2494 .- 1879-1425. ; 149, s. 647-649
-
Tidskriftsartikel (refereegranskat)abstract
- This project is devoted to the development of novel cellular vaccines designed to treat cancer patients. These cellular vaccines present and enhance immunogens, which will elicit a potent immune response. The goal is to achieve safe and effective immune reaction against the patient's own tumour. (1) Autologous cellular vaccines are prepared by processing circulating brood mononuclear cells outside of the patient's body (ex vivo) to differentiate them into antigen-presenting cells (APCs). Monocyte-derived APCs (MD-APCs) are then grown in the presence of exogenous target antigens (tumour cell debris, or apoptotic bodies) to become fully mature APCs. (2) Functionality for antigen presentation to T cells of ex vivo MD-APCs is evaluated in vivo. (3) Cellular vaccines are tested in selected rodent animal models. Efficiency and immune response are monitored in pertinent experimental systems for cancer. Pharmacological data are generated for clinical investigation. Tolerance and biologic effects are documented in primates. (4) The first clinical trials on cancer patients are taking place in 1998 on melanoma and prostate cancer to validate the concept. Specialized eel processors with dedicated software and standardized controls are being developed and used for the preparation of cellular vaccines. (5) The evaluation of new non-viral vectors and the validation of new non-viral transfection methods of mononuclear cells with marker genes is in progress and will lead to the ex vivo transfection of genes coding for immunostimulating cytokines or for tumour antigens in MD-APCs. Efficiency will be validated in vitro and in animal models. The ex vivo and animal model studies validate the clinical relevance of this new cellular immunotechnology. Clinical validation of individual autologous cellular vaccines in specific indications for which no treatment is presently available will allow the development of cellular and gene immunotherapy for other types of cancers.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Malmsten, M, et al.
(författare)
-
Adsorption of apolipoprotein B at phospholipid model surfaces
- 1995
-
Ingår i: Journal of Colloid and Interface Science. - 0021-9797 .- 1095-7103. ; 172, s. 485-493
-
Tidskriftsartikel (refereegranskat)abstract
- The adsorption of apolipoprotein B (Apo B) at a series of surfaces was investigated with in situ ellipsometry. For silica and methylated silica, the adsorbed amount (G), the adsorbed layer thickness (del) and the mean adsorbed layer refractive index (nf) were obtained by a procedure involving studies of the bare substrate at two different ambient refractive indices, as well as four-zone averaging. The adsorbed amount of Apo B is much higher at silica than at methylated silica. Despite this, the adsorbed layer thickness is the same at the two surfaces, and the adsorbed layer formation proceeds similarly. In both cases, the adsorbed layer formation occurs through the adsorption of Apo B molecules in an essentially random orientation, the difference between silica and methylated silica being the number of molecules adsorbed per unit area. Furthermore, the adsorption of Apo B at phospholipid surfaces was investigated. It was found that the adsorption at phosphatidylcholine (PC) was quite limited, whereas that at phosphatidic acid (PA) was substantial. Studies with mixed PA/PC layers showed that the Apo B adsorption depends on the mixed phospholipid layer composition in an essentially linear fashion. Finally, mixed phospholipid layers of PC and ganglioside GM1, as well as phosphatidylinositol (PI) layers, showed a dramatic preferential adsorption of Apo B over, e. g. human serum albumin (HSA), IgG, fibronectin and fibrinogen.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Jing, Xiaona, et al.
(författare)
-
Delivery of siRNA Complexed with Palmitoylated alpha-Peptide/beta-Peptoid Cell-Penetrating Peptidomimetics : Membrane Interaction and Structural Characterization of a Lipid-Based Nanocarrier System
- 2016
-
Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:6, s. 1739-1749
-
Tidskriftsartikel (refereegranskat)abstract
- Proteolytically stable alpha-peptide/beta-peptoid peptidomimetics constitute promising cell-penetrating carrier candidates exhibiting superior cellular uptake as compared to commonly used cell-penetrating peptides (CPPs). The aim of the present study was to explore the potential of these peptidomimetics for delivery of small interfering RNA (siRNA) to the cytosol by incorporation of a palmitoylated peptidomimetic construct into a cationic lipid-based nanocarrier system. The optimal construct was selected on the basis of the effect of palmitoylation and the influence of the length of the peptidomimetic on the interaction with model membranes and the cellular uptake. Palmitoylation enhanced the peptidomimetic adsorption to supported lipid bilayers as studied by ellipsometry. However, both palmitoylation and increased peptidomimetic chain length were found to be beneficial in the cellular uptake studies using fluorophore-labeled analogues. Thus, the longer palmitoylated peptidomimetic was chosen for further formulation of siRNA in a dioleoylphosphatidylethanolamine/cholesteryl hemisuccinate (DOPE/CHEMS) nanocarrier system, and the resulting nanoparticles were found to mediate efficient gene silencing in vitro. Cryo-transmission electron microscopy (cryo-TEM) revealed multilamellar, onion-like spherical vesicles, and small-angle X-ray scattering (SAXS) analysis confirmed that the majority of the lipids in the nanocarriers were organized in lamellar structures, yet coexisted with a hexagonal phase, which is important for efficient nanocarrier-mediated endosomal escape of siRNA ensuring cytosolic delivery. The present work is a proof-of-concept for the use of alpha-peptides/beta-peptoid peptidomimetics in an efficient delivery system that may be more generally exploited for the intracellular delivery of biomacromolecular drugs.
|
|
| 9. |
- Malekkhaiat Häffner, S., et al.
(författare)
-
Composition effects on photooxidative membrane destabilization by TiO2 nanoparticles
- 2021
-
Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797. ; 584, s. 19-33
-
Tidskriftsartikel (refereegranskat)abstract
- Membrane interactions and photooxidative membrane destabilization of titanium dioxide (TiO2) nanoparticles were investigated, focusing on the effects of membrane composition, notably phospholipid headgroup charge and presence of cholesterol. For this, we employed a battery of state-of-the-art methods for studies of bilayers formed by zwitterionic palmitoyloleoylphosphatidylcholine (POPC) containing also polyunsaturated palmitoylarachidonoylphosphocholine (PAPC), as well as its mixtures with anionic palmitoyloleoylphosphatidylglycerol (POPG) and cholesterol. It was found that the TiO2 nanoparticles display close to zero charge at pH 7.4, resulting in aggregation. At pH 3.4, in contrast, the 6 nm TiO2 nanoparticles are well dispersed due to a strongly positive ζ-potential. Mirroring this pH dependence, TiO2 nanoparticles were observed to bind to negatively charged lipid bilayers at pH 3.4, but much less so at pH 7.4. While nanoparticle binding has some destabilizing effect alone, illumination with ultraviolet (UV) light accentuates membrane destabilization, a result of oxidative stress caused by generated reactive oxygen species (ROS). Neutron reflectivity (NR), quartz crystal microbalance (QCM), and small-angle X-ray scattering (SAXS) results all demonstrate that membrane composition strongly influences membrane interactions and photooxidative destabilization of lipid bilayers. In particular, the presence of anionic POPG makes the bilayers more sensitive to oxidative destabilization, whereas a stabilizing effect was observed in the presence of cholesterol. Also, structural aspects of peroxidation were found to depend strongly on membrane composition, notably the presence of anionic phospholipids. The results show that membrane interactions and UV-induced ROS generation act in concert and need to be considered together to understand effects of lipid membrane composition on UV-triggered oxidative destabilization by TiO2 nanoparticles, e.g., in the context of oxidative damage of bacteria and cells.
|
|
| 10. |
|
|
