128 results about "Diphtheria toxin" patented technology

The invention provides an overexpression porcine co-stimulatory 4-1BB vector and application thereof. PCR (polymerase chain reaction) amplification is performed on a left homologous arm and a right homologous arm of an intron 1 of a rosa26 gene, a 4-1BB regulatory sequence and an OCT4 specific promoter; the left homologous arm, a 4-1BB expression cassette, LoxP locus-contained Cre and Neo expression cassettes, the right homologous arm and negative selection DTA diphtheria toxin are connected in sequence to obtain a 4-1BB homologous recombinant vector p4BOCNDR; the vector and a CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated) targeting vector of sgRNA (small guide ribonucleic acid) containing the intron 1 of the specific targeting porcine rosa26 gene are transferred together into a porcine fetus fibroblast; by taking a positive cell as a donor cell and an oocyte as a recipient cell, a cloned embryo is obtained through a somatic cell nuclear transfer technique; the cloned embryo is transplanted into a porcine uterus for fetation to obtain a transgenic pig integrating a 4-1BB gene at the fixed point of a first intron of the rosa26 gene and automatically deleting a marker gene.

The disclosure relates to cancer ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. In particular, the disclosure relates to concatemeric mRNA cancer vaccines encoding several cancer epitopes on a single mRNA construct, i.e. poly-epitope mRNA constructs or poly-neo-epitope constructs. The disclosure further relates to p53 and KRAS mutations, as well as incorporation of immune enhancers such as STING, e.g. mRNA constructs further encoding an immune stimulator or adjuvant. The disclosure further relates to inclusion of universal T cell epitopes, such as tetanus or diphtheria toxins to elicit an enhanced immune response.

The present application relates to compositions of modified diphtheria toxin and fusion proteins containing modified diphtheria toxin that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome, as well as methods of making the compositions. The present application also relates to a polypeptide toxophore from a modified diphtheria toxin, where the modification is at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of an unmodified native diphtheria toxin. Also described are fusion proteins which contain a modified diphtheria toxin and a non-diphtheria toxin fragment which contains a cell binding portion. The modified diphtheria toxins described can be used for the treatment of a malignant disease or a non-malignant disease.

The present invention relates to the field of recombinant toxin protein production in bacterial hosts. In particular, the present invention relates to production processes for obtaining high levels of a recombinant CRM197, Diphtheria Toxin, Pertussis Toxin, Tetanus Toxoid Fragment C, Cholera Toxin B, Cholera holotoxin, and Pseudomonas Exotoxin A, from a bacterial host.

The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.

The present invention relates to methods and compositions of modified variants of diphtheria toxin (DT) that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome. One aspect of the present invention relates to a polypeptide toxophore from a modified DT, wherein the mutation is the substitution or deletion at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of native DT. Another aspect of the present invention relates to a fusion protein which comprises a modified DT and a non-DT fragment. Another aspect of the present invention relates to the use of modified DT for the treatment of cancer.

This invention relates to a method for preparing immunogen G17CRM197 containing diphtherin mutant CRM197 as carrier. The method comprises: crosslinking diphtherin mutant CRM197 with gastrin G17 through epsiv-maleimidyl caproic acid N-hydroxysuccinimide eater (EMCS). Diphtherin mutant CRM197 is used as a carrier, and has such advantages as high recovery rate and easy purification. The method has such advantages as high product crosslinking rate, short preparation time, and low cost. Immunogen G17CRM197 can be used as an effective component in therapeutic vaccines, or used in anti-tumor drugs with appropriate immunoadjuvants.

Immunogenic compositions, cancer vaccines and methods for treating cancer are provided. Compositions comprising: (a) a glycan such as Globo H or an immunogenic fragment thereof, wherein the glycan is conjugated with a carrier protein by a linker such as para-nitrophenyl; and (b) an adjuvant comprising glycolipid capable of binding CDId on a dendritic cell, such as an a-galactosyl-ceramide derivative, wherein the immunogenic composition induces an immune response that induces a higher relative level of IgG isotype antibodies as compared to IgM isotype antibodies, are provided. Immunogenic compositions comprising the carrier protein diphtheria toxin cross-reacting material 197 (DT-CRM 197) and the adjuvant C34 are provided. Antibodies generated by immunogenic compositions disclosed herein further neutralize at least one of the antigens Globo H, stage-specific embryonic antigen-3 (SSEA-3) and stage-specific embryonic antigen-4 (SSEA-4). Therapeutics against breast cancer stem cells comprising immunogenic compositions comprising Globo H, SSEA-3 or SSEA-4 conjugated with DT-CRM 197.

The present invention provides novel methods of producing diphtheria toxin. In particular, the present invention provides novel methods of producing nontoxic forms of diphtheria toxin, e.g., CRM197. The present invention also provides novel compositions comprising diphtheria toxin or nontoxic forms of diphtheria toxin, e.g., CRM197.

This invention discloses a method for preparing recombinant diphtherin and its application. The recombinant diphtherin comprises diphtherin DAB389, a linker peptide (Gly4Ser) 2, and alpha-melanocyte stimulating hormone. The method comprises: (1) preparing a gene fragment of DAB389(Gly4Ser)2-alpha-MSH and a leading peptide, constructing an expression plasmid containing the gene fragment, and transforming Escherichia coli; (2) inducing with IPTG to obtain the target protein, purifying, digesting with Xa factor, and separating to obtain DAB389(Gly4Ser)2-alpha-MSH fusion protein. The method has such advantages as easy purification, and high yield. The recombinant diphtherin has high activity, and can attack and kill malignant melanoma without injuring normal cells, thus can be used to treat malignant melanoma.

The invention relates to a preparation method of a group C meningococcal capsular polysaccharide conjugate vaccine. The preparation method comprises the following steps: conducting EDAC catalysis on group C meningococcal capsular polysaccharide and promoting covalent binding of the group C meningococcal capsular polysaccharide to a truss arm ADH (antidiuretic hormone), so that a polysaccharide derivative is prepared; then, promoting covalent binding of the polysaccharide derivative and carrier protein, namely diphtheria toxin avirulent mutant CRM197, under the action of the EDAC catalysis, so that a polysaccharide-protein conjugate is formed; and purifying and filtering the polysaccharide-protein conjugate, so that a stock solution of the group C meningococcal capsular polysaccharide conjugate vaccine is obtained. The vaccine can be used for preventing epidemic cerebrospinal meningitis and complications thereof in infants caused by group C meningococci.

The present invention provides compositions and methods for inhibiting abnormal cell growth. In particular, the invention provides nucleic acids encoding Diphtheria toxin fusion proteins comprising residues 1-388 of Diphtheria toxin, wherein the native furin cleavage site has been substituted for a matrix metalloproteinase or plasminogen activator cleavage site, and a heterologous polypeptide and the polypeptides encoded by such nucleic acids. In addition, the invention provides methods of treating cancer by administering such polypeptides.

A Corynebacterium diphtheriae culture medium for the production of diphtheria toxin and methods for producing the toxin are provided. The medium is substantially free of animal-derived products and comprises water, a carbohydrate source, a nitrogen source and a number of free amino acids in an initial concentration wherein the initial concentration of each free amino acid is not limiting for the production of the toxin.

The invention provides a human rotavirus VP8 recombinant protein. The amino acid sequences of the VP8 recombinant protein include an amino acid sequence of a human rotavirus VP8 protein (hereinafter referred to as VP8 protein) and an amino acid sequence of exogenous polypeptide. The isoelectric point of the exogenous polypeptide is less than or equal to 5. The invention also provides a human rotavirus vaccine prepared based on the VP8 recombinant protein. Compared with the prior art, the VP8 recombinant protein provided by the invention can be expressed by fusing the VP8 protein with negativecharge-containing amino acid polypeptide fragments in tetanus toxin and/or diphtheria toxin proteins, and the water solubility and yield of the rotavirus VP8 protein expressed by escherichia coli areimproved; and moreover, the obtained fused protein has good immune ability, and the prepared vaccine has good effect.