Abstract: Autophagy is the principal catabolic response to nutrient starvation. However, excessive autophagy can be cytotoxic or cytostatic, and contribute to cell death, but its mechanism of induction remains elusive. Here, it was demonstrated that prolonged arginine starvation by ADI-PEG20 induced an autophagy-dependent death of argininosuccinate synthetase 1 (ASS1)-deficient breast cancer cells. Consequently, arginine depleting agents such as ADI-PEG20 may be used in methods for killing one or more argininosuccinate synthetase 1 (ASS1)-deficient breast cancer cells. Further, abundance of ASS1 was either low or absent in more than 60% of 149 random breast cancer biosamples, which could be exploited as candidates for arginine starvation therapy.

Abstract: The present invention relates to cell-penetrating effector proteins of type III secretion system (T3SS)-containing bacteria of the genus Salmonella or Shigella and variants, fragments and immunmodulatory domains thereof, for use in immunotherapy. The present invention further relates to cell-penetrating effector proteins of type III secretion system (T3SS)-containing bacteria of the genus Salmonella or Shigella and variants, fragments and immunmodulatory domains thereof, for delivering cargo molecules into eukaryotic cells.

Abstract: The present invention includes a method for diagnosis and treatment and prevention of Alzheimer's Disease comprising obtaining a biological sample from a subject suspected of having Alzheimer's Disease; determining the level of expression of HSP 27, wherein a statistically significant increase in HSP27 protein expression in the sample as compared to a sample from a non-Alzheimer's patient is indicative that the subject has Alzheimer's Disease; and modifying the treatment of the subject as a result of the detection of Alzheimer's Disease by providing the subject with standard therapy or a single vector expressing an A?42 trimer peptide and optionally the addition of an A?42 peptide, which elicits an immune reaction against the A?42 peptide, thereby preventing the accumulation of A?42 peptide and therefore preventing or treating Alzheimer's Disease.

Abstract: The invention provides a VLP free of a viral genome comprising two or more display polypeptides, nucleic acid molecules, polymers of the nucleic acid, lipopolysaccharides, lipopeptides, peptidoglycans and/or small molecules.

Abstract: The present invention provides recombinant Listeria strains comprising an angiogenic factor, recombinant polypeptides comprising an angiogenic factor operatively linked to a polypeptide comprising a PEST-like sequence, recombinant nucleotide molecules encoding same, related vaccines, and immunogenic and therapeutic methods utilizing same.

Abstract: Disclosed are compositions of matter, methods, and protocols useful for treatment of cancer through induction of anti-angiogenic immune responses. The invention provides means of differentiating tumor cells directly into endothelial or endothelial-like cells and utilizing said cells as immunogens for the purpose of inducing immunity against blood vessels feeding tumors. In one embodiment glioma cells are cultured under hypoxic conditions in the presence of endothelial-differentiating factors. In another embodiment, PECAM-1 positive cells are derived from a tumor mass or cell line and utilized as an antigenic source to induce immunity towards tumor derived endothelial cells, endothelial-like cells, and tumor vascular channels.

Abstract: This invention relates to compositions and methods for immunotherapy of cancer. Specifically, a method of cancer immunotherapy is described which results in the systemic liquidation of both solid and metastatic tumors whereever they reside in the body. The compositions include activated allogeneic Th1 cells that when administered appropriately lead to liquidation of tumors. The method includes administering priming doses of the therapeutic composition, ablation of a selected tumor lesion along with intratumoral injection of the composition and then infusion of the therapeutic composition. These steps enable the systemic liquidation of tumors secondary to immune cell infiltration and leads to immune-mediated tumor eradication.

Abstract: The present invention relates to a vaccine/inhibitor combination comprising an RNA vaccine comprising at least one RNA comprising at least one open reading frame (ORF) coding for at least one antigen and a composition comprising at least one PD-1 pathway inhibitor, preferably directed against PD-1 receptor or its ligands PD-L1 and PD-L2. The present invention furthermore relates to a pharmaceutical composition and a kit of parts comprising the components of such a vaccine/inhibitor combination. Additionally the present invention relates to medical use of such a vaccine/inhibitor combination, the pharmaceutical composition and the kit of parts comprising such a vaccine/inhibitor combination, particularly for the prevention or treatment of tumor or cancer diseases or infectious diseases. Furthermore, the present invention relates to the use of an RNA vaccine in therapy in combination with a PD-1 pathway inhibitor and to the use of a PD-1 pathway inhibitor in therapy in combination with an RNA vaccine.

Abstract: The present invention discloses novel isolates of Neorickettsia risticii, compositions comprising such isolates, vaccines and methods for using such vaccines against Potomac Horse Fever.

Abstract: Disclosed are stable conjugate vaccine formulations for protection against Salmonella typhi, and methods of conjugation between Vi-polysaccharide of S. typhi to tetanus toxoid as the carrier protein, responsible for producing improved T-dependent immune response against Typhoid fever caused by Salmonella typhi. The methods disclosed in this invention and the resulting formulations are capable of inducing immunity against typhoid fever including in children below 2 years of age, through only a single injection to comprise a complete vaccination schedule.

Abstract: The disclosure provides for immunogenic compositions against Pigeon Fever, and methods for their use and preparation. The immunogenic compositions, in alternate embodiments, also include other equine pathogens.

Abstract: The invention relates to the use of a bacterial artificial chromosome (BAC) for the preparation of a vaccine, wherein the BAC comprises an inducible bacterial ori sequence for amplification of the BAC to more than 10 copies per bacterial cell. Plus a viral expression cassette comprising a cDNA of an attenuated RNA virus genome and comprising cis-regulatory elements for transcription of said viral cDNA in mammalian cells and for processing of the transcribed RNA into infectious viral RNA.

Abstract: Disclosed are compositions and methods related to recombinant arenaviruses and their use in vaccines for the treatment or prevention of an arenavirus infection.

Abstract: A method of vaccination or immunisation involving the use of a photosensitizing agent, an antigenic molecule, e.g. a vaccine component, and an agent which enhances the effect of photochemical internalization (PCI)-mediated vaccination is disclosed wherein the agent is a ligand for a Toll-like receptor (TLR), and irradiation is with light of a wavelength effective to activate the photosensitizing agent. Antigenic, e.g. vaccine compositions, useful in such a method are also disclosed along with a method of generating antigen presenting cells which may be used to generate an immune response based on introducing antigenic molecules, e.g. vaccine components, into cells to achieve antigen presentation. The invention also provides methods of achieving vaccination in a subject using such cells.

Abstract: The invention provides an agent comprising: a cyclic peptide comprising a T cell antigen peptide; wherein in cyclised form the T cell antigen peptide is not capable of eliciting a T cell response; and wherein the T cell antigen peptide is rendered capable of eliciting a T cell response by selective cleavage of one or more cleavage sites in the cyclic peptide. The agent may be used to prevent or treat a condition characterised by the presence of unwanted cells.

Abstract: Vaccination methods to control PCV2 infection with different PCV2 subtypes are disclosed. Specifically, a PCV2 subtype a (PCV2a) ORF2 proteins or immunogenic compositions comprising a PCV2a ORF2 protein are used in a method for the treatment or prevention of an infection with PCV2 of a different subtype, the reduction, prevention or treatment of clinical signs caused by an infection with PCV2 of a different subtype, or the prevention or treatment of a disease caused by an infection with PCV2 of a different subtype.

Abstract: The present invention provides a dried influenza vaccine preparation in which the activity of an influenza vaccine antigen can be stably maintained even when stored without strictly maintaining a low temperature, and which can be stably supplied. The present invention also provides a method of producing the dried influenza vaccine preparation. The present invention provides a dried influenza vaccine preparation containing an influenza vaccine antigen and a disaccharide, wherein the disaccharide is at least one selected from the group consisting of sucrose, maltose, palatinose, melibiose, isomalt, cellobiose, allolactose, isomaltose, sophorose, lactobionic acid, laminaribiose, xylobiose, turanose, gentiobiose, rutinose, kojibiose, nigerose, robinose, neohesperidose, sucralose, and maltitol.

Abstract: Disclosed herein are nanoparticles containing MERS virus proteins in polymer structures, and compositions containing the nanoparticles formulated for administration as immunogenic compositions. Also provided herein are vector constructs encoding the proteins, and host cells containing the vector constructs. The disclosure also includes methods of making the nanoparticles and administering them to vertebrates, including methods of inducing immune responses to MERS that reduce or prevent infection by the virus.

Abstract: Disclosed are methods of treatment of a subject, such as a method of vaccination, immunomodulation or gene therapy of a subject. These methods comprise administering to the subject a modified enveloped viral particle, wherein the modified enveloped viral particle has been obtained by a method comprising the steps of a) incubating a fluid containing enveloped viral particles with one or more reactants consisting of a hydrophilic target domain and a lipophilic membrane anchor domain, wherein the lipophilic membrane anchor domain becomes integrated into the lipid double layer of the envelope of the viral particle, wherein the hydrophilic target domain becomes exposed to the fluid; and b) separating enveloped modified viral particles from excessive reactants.

Abstract: Compositions and methods of use for desensitizing a subject to an allergen via regions of the oral mucosa are provided.

Abstract: The present invention provides recombinant protein carrying an epitope. The recombinant protein has a skeleton structure from carrier protein, and a low immunogenic protein epitope is imported through splicing, replacement, and/or insertion to at least one molecular surface amino acid residue area of the carrier protein. The carrier protein has at least one T cell epitope, and the recombinant protein can effectively excite immunoreaction of an organism to the low immunogenic protein epitope.

Abstract: The present invention addresses the problem of providing an antibody titer-increasing agent, such as an adjuvant, capable of sustaining an effect achieved by, for example, vaccination, which is an antibody titer-increasing agent such as an adjuvant that is safe, convenient and economical and can be easily taken irrespective of age, and a method for manufacturing the same. A method for increasing an antibody titer and a method for enhancing the effect of a vaccine, each method comprising using Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 or a culture thereof; and an antibody titer-increasing agent such as an adjuvant that comprises Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 or a culture thereof.

Abstract: Compositions and methods for treating MM are provided herein.

Abstract: Compositions and methods that include stabilized protein drugs are described. In addition, protein drug formulations that are more stable under ambient conditions are described. The formulations include one or more poly amino acid ligands of the protein drug.

Abstract: A method for identifying a molecule that binds an irradiated tumor in a subject and molecules identified thereby. In some embodiments, the method includes the steps of (a) exposing a tumor to ionizing radiation; (b) administering to a subject a library of diverse molecules; and (c) isolating from the tumor one or more molecules of the library of diverse molecules, whereby a molecule that binds an irradiated tumor is identified. Also provided are targeting ligands that bind an irradiated tumor and therapeutic and diagnostic methods that employ the disclosed targeting ligands.

Abstract: The present invention is directed toward the use of non-thermal plasma-treated liquids as treatment options for herpes keratitis.

Abstract: A method of using a compound in a phototherapy procedure includes administering to a subject in need of treatment a therapeutically effective amount of a thio-substituted nucleobase, nucleoside, nucleotide, and/or analogs thereof; and exposing the administered compound to electromagnetic radiation.

Abstract: This disclosure provides a range of tyrosine amino acid lipid compounds and compositions useful for drug delivery, therapeutics, and the diagnosis and treatment of diseases and conditions. The amino acid lipid compounds and compositions can be used for delivery of various agents such as nucleic acid therapeutics to cells, tissues, organs, and subjects.

Abstract: The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): wherein R3 and R4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.

Abstract: In some aspects, methacrylate co-polymers crosslinked with an enzymatically cleavable peptide linker are provided and may be used for the oral delivery of a therapeutic. The peptide linker may be cleavable by an enzyme in the small intestine and may allow for the delivery of a therapeutic protein or nucleic acid to the small intestine. Also provided are methods of using the polymers for the treatment of a disease.

Abstract: Biodegradable triblock copolymer compositions are provided which are useful in preventing and inhibiting bleeding and infection following surgery. The copolymers are reverse thermal gels in that when heated from a lower temperature to a higher temperature, they gel. These gels are useful in drug delivery when complexed with one or more, such as two or more active agents including one or more antibiotics, biofilm inhibitors, procoagulants, and/or analgesics. For example the compositions can be used for injection of active agents, such as antibiotics, procoagulants and analgesics for prevention and/or inhibition of bleeding or infection following surgery. In one example, the disclosed compositions are combined with at least one biofilm inhibitor to prevent and/or inhibit post surgical infection caused by biofilms.

Abstract: Disclosed herein are glycidol-based polymers, nanoparticles, and methods related thereto useful for drug delivery. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Method for preparing a supramolecular therapeutic agent delivery assembly are provided. A carbonate-containing precursor, a functionalized aliphatic precursor, and an aromatic diamine precursor may be combined to form an amphiphilic block co-polymer. The block co-polymer undergo a cross-linking polymerization process and a therapeutic agent may be incorporated into the resulting supramolecular assembly. The supramolecular assembly may comprise HT, PHT, HA, and/or PHA materials.

Abstract: Porous soy protein-based scaffolds and methods for making the scaffolds using 3D printing techniques are provided. Also provided are tissue growth scaffolds comprising the porous soy protein-based scaffolds and methods for growing tissue on the tissue growth scaffolds. The porous soy protein-containing scaffold comprises a plurality of layers configured in a vertical stack, each layer comprising a plurality of strands comprising denatured soy proteins.

Abstract: Synthetic design of drug-incorporated novel dendrimer structures for quantitatively controlled drug delivery. The dendritic drugs have better control and thus a quantitative drug release can be obtained. There are no prior art dendritic drugs that control release both sequentially and quantitatively like the dendritic drugs disclosed herein. The dendritic drugs are formed by incorporating multiple same type drug units or more than two different drug types into a dendritic cascade structure to form a dendrimer drug.

Abstract: The present disclosure is directed to compositions comprising templated nanoconjugates and methods of their use.

Abstract: Methods of conjugating two molecules are disclosed herein in which a non-polymeric aliphatic dialdehyde or non-polymeric aromatic dialdehyde is reacted with a compound comprising an amine (NH2) moiety to form a stable product under mild conditions.

Abstract: Cholesterol moieties are linked to specific ends of double-stranded RNA, preferably a small, interfering (si)RNA or to a dsHybrid. The dsHybrid has one strand comprised of DNA and one strand comprised of RNA. Preferably the sense strand is the DNA strand and the antisense strand is the RNA strand of the dsHybrid. The present invention is based upon the discovery that a cholesterol moiety, if linked to a specific end or ends of the sense or antisense strands of a siRNA, can enhance the delivery and silencing efficiency of the siRNA directed against its target message, in comparison with a corresponding, non-conjugated siRNA. Conjugated siRNAs and dsHybrids of the invention are optionally formulated with, or coordinately administered with, a secondary delivery-enhancing agent, such as a delivery-enhancing peptide, to enhance intracellular delivery and uptake of the conjugated siRNAs or dsHybrid.

Abstract: Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

Abstract: A novel monomer design for the synthesis of PPE-type polymers containing conjugated segments of well-defined length connected by flexible linkers under Sonogashira reaction conditions is presented. The resulting polymers retain the photophysical properties of a fully conjugated PPE. The extent of incorporation of the flexible units along the backbone is governed by the comonomer feed ratio and can be varied in a statistically predictable fashion.

Abstract: Disclosed is a protein aqueous suspension preparation containing a protein and a polyamino acid, the protein and the polyamino acid having a surface charge in a buffer and forming a complex suspended in the buffer, wherein the absolute value of the difference between pH of the buffer and isoelectric point pI of the protein is in the range of from 0.5 to 4.0. Also disclosed are a method of preparing a protein aqueous suspension preparation and a prefilled syringe containing a concentrated protein aqueous suspension preparation. The protein can exhibit at least one of shaking stress resistance, fluidity enhancement, oxidation resistance, thermal stability, and aggregation inhibitory properties.

Abstract: To study RNA function using small molecules, we designed bioactive, modularly assembled small molecules that target the noncoding expanded RNA repeat that causes myotonic dystrophy type 1 (Dm1), r(CUG)exp. Different modular assembly scaffolds were investigated including polyamines, alpha-peptides, beta-peptides, and peptide tertiary amides (PT As). Based on activity as assessed by improvement of DM1-associated defects, stability against proteases, cellular permeability, and toxicity, we discovered that constrained backbones, namely PT As, are optimal.

Abstract: The present disclosure provides various molecular constructs having a targeting element and an effector element. Methods for treating various diseases using such molecular constructs are also disclosed.

Abstract: Provided is a method of treating a wound site. Also provided is a system for treating a wound site. Additionally provided is the use of reduced pressure and a nucleic acid that promotes wound healing for treatment of a wound site. Further provided is the use of a nucleic acid that promotes wound healing for the manufacture of a medicament for treating a wound site that is undergoing reduced pressure treatment.

Abstract: The present application describes a coding nucleic acid sequence, particularly a messenger RNA (mRNA), comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal and the use thereof for increasing the expression of an encoded protein. It also discloses its use for the preparation of a pharmaceutical composition, especially a vaccine e.g. for the use in the treatment of tumours and cancer diseases, cardiovascular diseases, infectious diseases, autoimmune diseases or genetic diseases, or in gene therapy. The present invention further describes an in vitro transcription method, in vitro methods for increasing the expression of a protein using the nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal and an ex vivo and in vivo method.

Abstract: A method includes: (1) applying stimulations to a system, wherein applying the stimulations includes modulating, over time, characteristics of the stimulations; (2) measuring a time-varying response of the system to the stimulations; (3) fitting the time-varying response of the system into a model of the system; and (4) using the model of the system, identifying an optimized combination of characteristics of the stimulations to yield a desired response of the system.

Abstract: The present invention provides dichromic fluorescent compounds, as well as processes for making and methods for using the dichromic fluorescent compounds.

Abstract: The present invention provides a safe polymer nanoparticle composite with few side effects, and an MRI contrast agent incorporating said polymer nanoparticle composite. The polymer nanoparticle composite is capable of specifically accumulating on a tumor tissue to selectively extract the tissue, exhibiting high contrast even when used in small amounts, and enabling imaging over prolonged periods of time. This polymer nanoparticle composite is characterized by containing a block copolymer that includes a non-charged hydrophilic polymer chain segment and an anionic polymer chain segment, and MnCaP.

Abstract: Surface conjugated diamagnetic Chemical Exchange Saturation Transfer (diaCEST) agent carriers and methods of making and using are described herein. The particles are safe alternatives to conventional paramagnetic or superparamagnetic metal-based MRI contrast agents that are often toxic and therefore not biocompatible. The carriers described herein can provide simultaneous monitoring of multiple particle types labeled with ‘multicolor’ diaCEST contrast agents. In some embodiments, the carriers are micro- and/or nanoparticles. In other embodiments, the carriers are liposomes. In some embodiments, the particles and/or liposomes are mucus penetrating. In other embodiments, the particles and/or liposomes are not mucus penetrating.

Abstract: Methods and suspensions are provided that are useful for preparing readily reconstitutable, dry compositions of micro- or nanospheres. The dry compositions find use in diagnostic applications such as ultrasonic imaging. The suspension includes as key ingredients one or both of t-butyl alcohol and/or an amorphous sugar (or mixture of amorphous sugar) in specified amounts that reduce aggregation of the particles comprising the suspension.