Linear and Branched Glyco-Lipopeptide Vaccines Follow Distinct Cross-Presentation Pathways and Generate Different Magnitudes of Antitumor Immunity

Glyco-lipopeptides, a form of lipid-tailed glyco-peptide, are currently under intense investigation as B- and T-cell based vaccine immunotherapy for many cancers. However, the cellular and molecular mechanisms of glyco-lipopeptides (GLPs) immunogenicity and the position of the lipid moiety on immunogenicity and protective efficacy of GLPs remain to be determined.We have constructed two structural analogues of HER-2 glyco-lipopeptide (HER-GLP) by synthesizing a chimeric peptide made of one universal CD4(+) epitope (PADRE) and one HER-2 CD8(+) T-cell epitope (HER(420-429)). The C-terminal end of the resulting CD4-CD8 chimeric peptide was coupled to a tumor carbohydrate B-cell epitope, based on a regioselectively addressable functionalized templates (RAFT), made of four alpha-GalNAc molecules. The resulting HER glyco-peptide (HER-GP) was then linked to a palmitic acid moiety, attached either at the N-terminal end (linear HER-GLP-1) or in the middle between the CD4+ and CD8+ T cell epitopes (branched HER-GLP-2). We have investigated the uptake, processing and cross-presentation pathways of the two HER-GLP vaccine constructs, and assessed whether the position of linkage of the lipid moiety would affect the B- and T-cell immunogenicity and protective efficacy. Immunization of mice revealed that the linear HER-GLP-1 induced a stronger and longer lasting HER(420-429)-specific IFN-gamma producing CD8(+) T cell response, while the branched HER-GLP-2 induced a stronger tumor-specific IgG response. The linear HER-GLP-1 was taken up easily by dendritic cells (DCs), induced stronger DCs maturation and produced a potent TLR- 2-dependent T-cell activation. The linear and branched HER-GLP molecules appeared to follow two different cross-presentation pathways. While regression of established tumors was induced by both linear HER-GLP-1 and branched HER-GLP-2, the inhibition of tumor growth was significantly higher in HER-GLP-1 immunized mice (p<0.005).These findings have important implications for the development of effective GLP based immunotherapeutic strategies against cancers

Synthesis and cross-linking of bifunctional monomers containing carbazole moieties

New bifunctional carbazolyl-containing monomers were synthesized and their cationic photo-initiated polymerization investigated. The monomers containing two reactive groups such as epoxy, oxetanyl and vinyloxyethyl, were prepared from commercially available 9-(2,3-epoxypropyl)carbazole. The kinetics of UV curing of the monomers was monitored by real-time FT-IR technique. The type of functionality was found to have a considerable influence on the photo-curing rate, but has not an evident effect on the final reactive group conversion. The cross-linked systems were found to have low glass transition temperatures ranging from 7 to 10 °C. Electron photoemission spectroscopy revealed ionization potentials of 5.75–5.8 eV for the thin cross-linked layers of the monomersKauno technologijos universiteta

Triplet states and energy back transfer of carbazole derivatives

Intermolecular interactions among π conjugated semiconducting molecules often give rise to totally different optical behaviours between the solid state and dilute phases. Phosphorescence spectra observed in the solid state are often lowered compared with dilute forms resulting in the red-shift of the phosphorescence spectra. Here, we demonstrate that this red-shift can be reduced by introducing side groups. We also show that such a shift is a function of interchromophoric distance with fast exponential decay. Furthermore, we show conclusively that triplet exciton transfer between the hosts and the bis[2-(4F,6-difluorophenyl)pyridinato-C2,N](picolinato)iridium(iii) can be described in terms of the Boltzmann factor using triplet energies obtained from the solid state. These results will have implications in molecular design that utilizes triplet excitons such as organic light emitting diodes and singlet fission solar cells

Energy Structure and Electro-Optical Properties of Organic Layers with Carbazole Derivative

Phosphorescent organic light emitting diodes are perspective in lighting technologies due to high efficient electroluminescence. Not only phosphorescent dyes but also host materials are important aspect to be considered in the devices where they are a problem for blue light emitting phosphorescent molecules. Carbazole derivative 3,6-di(9-carbazolyl)-9-(2-ethylhexyl)carbazole (TCz1) is a good candidate and has shown excellent results in thermally evaporated films. This paper presents the studies of electrical properties and energy structure in thin films of spin-coated TCz1 and thermally evaporated tris[2-(2,4-difluorophenyl)pyridine]iridium(III) (Ir(Fppy)3). The 0.46 eV difference of electron conduction level between TCz1 and Ir(Fppy)3 compounds was obtained from the cyclic voltammetry and photoconductivity measurements. Temperature modulated space charge limited current (TM-SCLC) method is used to measure the local trapping states for charge carrier in the energy gap. The TM-SCLC measurements for the system TCz1 + 8 wt.% Ir(Fppy)3 show a trapping state with the value of 0.4 eV which is comparable to the conduction level difference of these materials. It allows to conclude that Ir(Fppy)3 molecules act as electron traps in the TCz1 matrix and the TM-SCLC method is applicable to investigate dopants as trapping states. To show the trap effect, an organic light emitting diode was made where the electroluminescent layer was a spin-coated host-guest system of TCz1 with incorporated 8 wt.% Ir(Fppy)3