DNA fusion vaccines against B-cell tumors Zhu, Delin; Rice, Jason; Savelyeva, Natalia ...
Trends in Molecular Medicine,
12/2001, Letnik:
7, Številka:
12
Book Review, Journal Article
Recenzirano
DNA vaccination is currently being explored as a potential strategy for combatting cancer. However, tumor antigens are often weak and the immune system of patients may be compromised. For B-cell ...tumors, immunoglobulin idiotypic antigens provide defined targets but are poorly immunogenic. Fusion of a sequence derived from tetanus toxin to the genes encoding idiotypic determinants has proved highly effective in activating protective anti-tumor immunity. DNA fusion vaccines containing immuno-enhancing sequences can augment and direct immune attack on a range of target antigens. Gene-based fusion vaccines offer ease of manipulation and flexible design to activate effective attack on cancer.
DNA fusion vaccines consisting of a sequence derived from tetanus toxin fused to genes encoding idiotypic determinants have proven very effective against B-cell tumors
Chapter 11 - Cancer Vaccines Stevenson, Freda K.; Genova, Gianfranco di; Ottensmeier, Christian ...
Cancer Immunotherapy,
2007
Book Chapter
This chapter focuses on the problems faced in attempting to induce the effective therapeutic immunity, and describes the promising strategies that might be employed to overcome these difficulties. ...The rational design of vaccines based on the existing immunological knowledge is also provided. Vaccines against the cancer-associated pathogens, such as the human papilloma virus (HPV) or the hepatitis B virus (HBV), are successful in preventing the associated cancers. The success of the passive immunotherapy with monoclonal antibodies or via the allogeneic transplantation show that the immune system is capable of attacking the cancer cells. An understanding of the balances in the immune system and of the evasion tactics is the key to effective vaccination and can inform new vaccine designs. However, the cancer vaccines are required to solve the poor immunogenicity problem of the majority of cancer antigens. This can be overcome by the cautious borrowing of immunogenic molecules from pathogens.
The research concerns the changing requirements to a new generation of experts demanded by Industry 4.0. Rapid technological development of the enterprises, digitalization of their processes ...galvanize the universities to adapt their approaches to both students, training technology and quality control management. Moreover, we compared manufacturing process with the educational one, analyzing the possibilities of the currently developed teaching technology to comply with the enterprises' demands.
Phytoplankton is the base of the marine food chain as well as oxygen and carbon cycles and thus plays a global role in climate and ecology. Nucleocytoplasmic Large DNA Viruses that infect ...phytoplankton organisms and regulate the phytoplankton dynamics encompass genes of rhodopsins of two distinct families. Here, we present a functional and structural characterization of two proteins of viral rhodopsin group 1, OLPVR1 and VirChR1. Functional analysis of VirChR1 shows that it is a highly selective, Na
/K
-conducting channel and, in contrast to known cation channelrhodopsins, it is impermeable to Ca
ions. We show that, upon illumination, VirChR1 is able to drive neural firing. The 1.4 Å resolution structure of OLPVR1 reveals remarkable differences from the known channelrhodopsins and a unique ion-conducting pathway. Thus, viral rhodopsins 1 represent a unique, large group of light-gated channels (viral channelrhodopsins, VirChR1s). In nature, VirChR1s likely mediate phototaxis of algae enhancing the host anabolic processes to support virus reproduction, and therefore, might play a major role in global phytoplankton dynamics. Moreover, VirChR1s have unique potential for optogenetics as they lack possibly noxious Ca
permeability.
Factor Xa (FXa) is known to play a central role in blood coagulation cascade and considered to be one of the most attractive targets for oral anticoagulants of new generation.
Our approach for the ...development of directly acting oral anticoagulants (DOAC), FXa inhibitors was demonstrated in this work.
Chemical synthesis is the base of our approach for the development of potential inhibitors. In this work, the substances like R1-(CONH)-R2-(CONH)-R3 are being developed, using previously described docking and screening methods, where R1, R2 and R3 are some chemical groups and (CONH) are amide bonds connecting R1, R2 and R3. The direction of amide bond (CONH) could be arbitrary for R1, R2 and R2, R3.
Chemical modifications were made in the frame of the results, taking into account the structure of FXa, chemical synthesis capabilities, as well as patentability of the target compounds. Subnanomolar potency of several developed compounds was achieved. Several analyzers and various testing-suites have been used to measure the concentration that doubled the prothrombin time (PTx2). Moreover, in human plasma the PTx2 concentration of the compound 217 (DD217) turned out to be 80±20 nM. The compound efficacy has proved by in vivo assays including oral administrations in rats, rabbits and monkeys.
The pharmacodynamic profile of DD217 for oral administration in cynomolgus monkeys proves the efficacy of the compound, which makes it promising for the future preclinical trials.
The geochemical variations of magmas across and along supra-subduction zones (SSZ) have been commonly attributed to profound changes in the phase and chemical compositions of the mantle source and ...subduction-derived melt and fluid fluxes, as well as the physical parameters (e.g. depth, temperature, oxygen fugacity etc) of slab dehydration, mineral breakdown and melting. Here we test the variability of the Late Quaternary primitive magmas in the southern and northern parts of the meridionally oriented Eastern Volcanic Belt (EVB) of Kamchatka, with a slab depth varying from 60 to 160 km. Eight high-Mg (Mg# > 60 mol%) basalts were characterized for major, trace and platinum-group element (PGE) abundances, as well as the compositions of olivine phenocrysts and olivine-hosted spinel inclusions. The basalts in our study are geochemically typical of SSZ magmas and contain similar liquidus assemblages of forsteritic olivine (Mg# 78–92 mol%), low-Ti Cr-spinel and clinopyroxene. Although the absolute abundances of major and trace elements, and their ratios, in the basalts fluctuate to some extent, the observed variability cannot be correlated with any of considered parameters in the geometry of the Kamchatka SSZ and conditions of melting. This unexpected result led to the evaluation of the platinum-group element (PGE) systematics against the lithophile and chalcophile trace element geochemistry and the compositions of phenocrysts. Total whole-rock PGE content varies from 2.3 to 11.7 ppb, whereas the normalized PGE concentration patterns are typical for supra-subduction zones magmas and broadly similar in all studied samples. They are enriched in Rh, Pd and Pt relative to mid-ocean ridge basalts (MORB) and have nearly identical concentrations of Ir-group PGE. The only parameter that correlates well with PGE contents is the average Mg# of olivine phenocrysts from 84 to 90.3 mol%. This is interpreted to result from minor cryptic fractionation of sulfide melt, together with primitive olivine, in low-to-mid crustal conditions. Negative Ru anomalies on chondrite-normalized diagrams correspond to the Fe2+/Fe3+ ratios in spinel (a proxy for magma redox conditions), which reflects a replacement of monosulfide solid solution by laurite in the mantle wedge during oxidation.
•Most magnesian basalts in eastern Kamchatka arc represent primitive magmas.•No correlation found between arc system geometry and geochemistry and mineralogy.•PGE contents and systematics in studied high-Mg basalts are typical of arc magmas.•Local sulfide saturation is a common feature for primitive magmas of Kamchatka.•Laurite is a restite mineral in the sub-arc mantle that produces negative Ru anomalies.
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