15 results about "Diphtheria toxin" patented technology

The present invention provides a method for treating or inhibiting a myeloproliferative tumor (MPN) in a subject in need thereof, the method comprising administering to the subject a diphtheria toxin-human interleukin-3 conjugate (DT-IL3) and one or more Jak inhibitors and / or one or more hypomethylating agents.

The invention discloses a pharmaceutical composition and application thereof, the pharmaceutical composition comprises a recombinant protein and an HIV virus invasion inhibitor, and the recombinant protein comprises: 1) an scFV of an anti-CD3 antibody; and 2) diphtheria toxin.

The present disclosure provides, in part, a method of treating an autoimmune disease in a subject by reducing the number of pDCs through administration of a human interleukin-3 (IL-3)-diphtheria toxin conjugate (DT-IL3). The disclosure also generally relates to methods of monitoring the effectiveness of therapy in subjects receiving DT-IL3 for treating an autoimmune disease, and methods of determining continuing treatment of subjects receiving DT-IL3 for treating an autoimmune disease. The disclosure also provides pharmaceutical compositions of DT-IL3 for use in such methods.

This disclosure relates to immunotoxin fusion proteins that comprise a bivalent single-chain fragment variable that specifically binds to the thrombopoietin receptor (cMPL); and a diphtheria toxin. The disclosure also provides compositions comprising such proteins and nucleic acid molecules encoding such proteins and uses thereof.

The invention relates to preparation and application of an engineering virus with high tumor specificity and high killing efficiency. Specifically, the invention relates to a recombinant oncolytic virus based on HSV-1 transformation, which is mainly characterized in that a diphtheria toxin A subunit (DT-A) expression cassette driven by a tumor specific promoter (such as Survivin) is inserted into an ICP6 gene coding region of wild type HSV-1, so that specific recognition and efficient direct killing of tumor cells are realized, and the expression cassette is a recombinant oncolytic virus. And hepatic targeting delivery is realized by matching with red blood cells treated by cationic polymers.

The invention discloses teasel glycosyl transferase and application thereof in production of alpha-hederaoside and teasel saponin B. The amino acid sequence of the teasel glycosyl transferase is shown as SEQ ID NO.1, and the nucleotide sequence of the coding gene of the teasel glycosyl transferase is shown as SEQ ID NO.2. The invention further discloses a preparation method of the teasel glycosyl transferase. After the glycosyl transferase is subjected to prokaryotic expression, a series of triterpenoid saponins can be catalyzed to be converted into triterpenoid saponin-3-(2-O)-glycoside products in a glycosylation manner, and the triterpenoid saponin-3-(2-O)-glycoside products comprise alpha-hederin and dipsacus asper saponin B. The discovery of the dipsacus asper triterpenoid saponin glycosyltransferase provides more optional biological elements for the biosynthesis of natural products, and has a good application prospect.

EVs are being recognized as vectors for drug delivery. In particular. EV loading with targeting and therapeutic agents brings along an interesting opportunity to translate EVs into a bio-mimetic selective delivery system. Indeed. EVs constitute a physiological carrier being potentially less immunogenic than artificial delivery vehicles. The inventors now developed a novel method to control the loading of a cargo into EVs on demand. These EVs are equipped, if necessary, with non-viral fusogen, therefore enhancing EV-cargo delivery into acceptor cells. To acutely measure this process, they follow the fate of a luciferase-tagged cargo. Cargo loading was enabled through a drug-reversible inducible dimerization system. Briefly, donor cells were transfected with plasmids encoding for FKBP-tagged CD63, a classical membrane EV marker, and FRB-Nanoluciferase (NLuc) that is normally cytosolic. Upon addition of the dimerizing drug. FRB-Nluc interacts with FKBP-CD63 and is recruited into secreted EVs. This is accompanied by an enhanced delivery into acceptor cells. This phenomenon can be further enhanced when EVs are equipped with syncitin1, a mammalian fusogenic protein that trigger fusion between EV membrane and the plasma membrane of acceptor cells. Using this novel process, the inventors further demonstrated that the catalytic domain of the Diphteria toxin (DTA), that is responsible for protein synthesis inhibition and ultimately cell death, can be delivered to acceptor cells via functionalized EVs. This led to protein synthesis inhibition and death of acceptor cells. This novel method and the derived applications promise to open new doors in precision care medicine, especially when EVs will be equipped with antibodies raised against cell specific antigens.

Cytotoxin-CCL8 peptide constructs that include a cytotoxin linked to a CCL8 peptide and uses thereof. The cytotoxin can include a cytotoxic peptide such as a diphtheria toxin peptide. The constructs can be used to treat CCL8-related diseases, such as cancer, graft versus host disease (GVHD), microbial infections, and pulmonary fibrosis acute respiratory distress syndrome (ARDS), among others.

The application discloses a fermentation process of gonadotropin-releasing hormone hexamer-diphtheria toxin mutant CRM197, and the process comprises the following steps: screening of a fermentation medium and optimization of fermentation conditions. The fermentation medium comprises yeast extract powder, tryptone and NaCl, and the optimization of the fermentation process comprises culture temperature, an inducing agent, concentration of the inducing agent, culture time after induction, adjustment mode of pH of the fermentation liquor, stirring speed, ventilation amount and the like. The fermentation process has the advantages of low production cost, short production cycle (only 12-15 hours are needed), improved expression amount of the target protein per unit of bacteria, and realized high-efficiency expression of the target protein. The GnRH6-CRM197 prepared by the application can be used for immunocastration of various mammals, and has the values of further research and development and good industrialization prospect.

The present invention provides a method for constructing an animal model of neurotrophic keratitis and its application, and relates to the technical field of animal models. Cre Mice were co-housed with ROSA26i-DTR mice, and the offspring were genotyped. After screening for TRPV1-DTR double-heterozygous mice, these TRPV1-DTR mice were intraperitoneally injected with diphtheria toxin. Twenty-one days after treatment, a mouse model of neurotrophic keratitis was established. This invention, developed using widely used experimental mice, is the first genetic NK model. The model is simple, stable, and has a short lifespan. It aligns with clinical staging and meets clinical disease progression criteria.

The present invention refers to a fusion protein or conjugate comprising or consisting of: a) a Diphtheria toxin deprived of the receptor binding domain or functional fragments or derivatives or a biologically active variant thereof; and b) at least one surface immunoglobulin (sIg) B-cell targeting peptide or functional fragments or derivatives or a biologically active variant thereof. Isolated nucleic acids, vectors and pharmaceutical compositions related to said fusion protein, as well as their medical uses, are also objects of the invention.

The present invention provides an anti-diphtheria toxin mutant antibody, its preparation method, and application. The anti-diphtheria toxin mutant antibody (anti-CRM197 antibody) obtained through screening has high affinity for free CRM197 but weak affinity for conjugated CRM197, resulting in good discrimination. Therefore, it can be used to detect the content of free CRM197 in CRM197 conjugate vaccines. Based on this, a method has been developed for quantitatively detecting the content of unconjugated CRM197 in conjugate vaccines using CRM197 as a carrier protein, thereby establishing a quality control method for the free CRM197 content in CRM197 conjugate vaccines.

The invention provides a CRM197 protein variant and application thereof. According to the variant, arginine at the 458th site is mutated into proline, proline at the 225th site is mutated into glutamic acid, and glycine at the 510th site is mutated into aspartic acid. The CRM197 protein variant has excellent stability, can stably exist in an environment of 37 DEG C / 50 DEG C and is free of precipitation and degradation loss, the immunogenicity of the CRM197 protein variant is remarkably improved compared with that of CRM197, antigen presenting cells with a higher proportion can be stimulated and activated, and stronger specific humoral immunity, cellular immunity and immune memory can be stimulated in vivo. In addition, the CRM197 protein variant has good anti-tumor activity, and can significantly inhibit the amplification of ovarian tumors. The invention also provides application of the CRM197 protein variant in preparation of diphtheria toxin vaccines, antigen carrier proteins and tumor treatment drugs.

Provided is an E. coli cell for the production of a Diphtheria toxin polypeptide or mutated form thereof, such as the toxoid CRM197 polypeptide. The E. coli's endogenous gene encoding leucine / isoleucine / valine transporter subunit (LivK) is disrupted, deleted, or engineered to encode an affinity tag fused to the LivK and / or the E. coli's endogenous gene encoding maltose transporter subunit (MalE) is disrupted, deleted, or engineered to encode an affinity tag fused to the MalE to facilitate purification of the Diphtheria toxin polypeptide or mutated form thereof from the E. coli.

EVs have been recognized as vectors for drug delivery. In particular, loading EVs with targeting and therapeutic agents offers intriguing opportunities for converting EVs into biomimetic selective delivery systems. Indeed, EVs constitute physiological carriers that are potentially less immunogenic than artificial delivery vehicles. Here, we developed a novel method for on-demand controlled cargo loading into EVs. These EVs are equipped with nonviral fusogenic factors, as needed, thus facilitating the delivery of EV-cargo to acceptor cells. To sensitively measure this process, we tracked the fate of luciferase-tagged cargo. Cargo loading was enabled by a drug-reversible, inducible dimerization system. Briefly, donor cells were transfected with plasmids encoding FKBP-tagged CD63, a classical membrane EV marker, and FRB-Nanoluciferase (NLuc), a normally cytoplasmic protein. Upon addition of a dimerizer, FRB-Nluc interacts with FKBP-CD63 and is recruited to secreted EVs, which promotes delivery to acceptor cells. This phenomenon can be further enhanced if EVs are equipped with syncytin 1, a mammalian fusogenic protein that induces fusion between the EV membrane and the plasma membrane of acceptor cells. Using this novel method, we further demonstrated that the catalytic domain of diphtheria toxin (DTA), which is involved in protein synthesis inhibition and ultimately cell death, can be delivered to acceptor cells via functionalized EVs. This resulted in protein synthesis inhibition and death of the acceptor cells. This novel method and its resulting applications are expected to open new doors in precision medicine, especially when EVs are equipped with antibodies raised against cell-specific antigens.