182 results about "Exotoxin" patented technology

The present invention mainly provides a fusion antigen specific for a target cell comprising a ligand moiety which is capable of reacting, recognizing or binding to the receptors on the target cell, a Pseudomonas exotoxin A translocation domain II, an antigenic moiety, and a carboxyl terminal moiety which permits combination of the fusion antigen to the endoplasmic reticulum (ER) membrane of the target cell. A method of immunizing an animal using the fusion antigen is also provided.

Recombinant immunotoxins are fusion proteins composed of the Fv domains of antibodies fused to bacterial or plant toxins. RFB4 (Fv)-PE38 is an immunotoxin that targets CD22 expressed on B cells and B cell malignancies. The present invention provides antibodies and antibody fragments that have improved ability to bind the CD22 antigen compared to RFB4. Immunotoxins made with the antibodies and antibody fragments of the invention have improved cytotoxicity to CD22-expressing cancer cells. Compositions that incorporate these antibodies into chimeric immunotoxin molecules that can be used in medicaments and methods for inhibiting the growth and proliferation of such cancers. Additionally, the invention provides a method of increasing the cytotoxicity of forms of Pseudomonas exotoxin A (“PE”) with the mutation of a single amino acid, as well as compositions of such mutated PEs, nucleic acids encoding them, and methods for using the mutated PEs.

Methods and compositions relating to recombinant anti-CD22 antibodies with high binding affinity, and immunoconjugates comprising the anti-CD22 antibody linked to a therapeutic agent such as a Pseudomonas exotoxin or a detectable label. The invention provides diagnostic methods, and means to inhibit the growth of malignant B cells.

A method and apparatus for preventing and treating septicemia in patient blood. The extracorporeal system includes an anti-microbial device to kill at least 99% of bloodborne microorganisms, a hemoconcentrator / filtration unit to remove approximately 90% of target molecules from the patient blood and a filter unit to remove target molecules from patient blood from the sieved plasma filtrate. Target molecules are produced by microorganisms as well as the patient's cells and include endotoxins from gram negative bacteria, exotoxins from gram negative and gram positive bacteria, as well as RAP protein mediator from Staphylococcus aureus, and cell mediators such as tumor necrosis factor-alpha, and interleukin 1-beta, complement proteins C3a and C5a, and brandykinin.

An immunotoxin for use in, and a method for treating a subject having a cancer associated with malignant B-lineage cells or an autoimmune condition, are disclosed. The immunotoxin includes (a) an anti-CD19 antibody lacking an Fc fragment, (b) a modified exotoxin A protein having both Domains II and III, but lacking Domain I, and (c) a peptide linker joining the C-terminal end of the antibody to the N-terminal end of the modified exotoxin A protein. The linker is substantially resistant to extracellular cleavage. The modified exotoxin A protein may be further modified to include a C-terminal KDEL sequence (SEQ ID NO: 6) that promotes transport of the protein to the endoplasmic reticulum of cells that have taken up the immunotoxin.

The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and / or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.

Recombinant immunotoxins are fusion proteins composed of the Fv domains of antibodies fused to bacterial or plant toxins. RFB4 (Fv)-PE38 is an immunotoxin that targets CD22 expressed on B cells and B cell malignancies. The present invention provides antibodies and antibody fragments that have improved ability to bind the CD22 antigen compared to RFB4. Immunotoxins made with the antibodies and antibody fragments of the invention have improved cytotoxicity to CD22-expressing cancer cells. Compositions that incorporate these antibodies into chimeric immunotoxin molecules that can be used in medicaments and methods for inhibiting the growth and proliferation of such cancers. Additionally, the invention provides a method of increasing the cytotoxicity of forms of Pseudomonas exotoxin A (“PE”) with the mutation of a single amino acid, as well as compositions of such mutated PEs, nucleic acids encoding them, and methods for using the mutated PEs.

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.

A transcutaneous immunization system delivers antigen to immune cells through the skin, and induces an immune response in an animal or human. For example, a skin-active adjuvant (e.g., an ADP-ribosylating exotoxin) can be used to induce an antigen-specific immune response (e.g., humoral and / or cellular effectors) after transcutaneous application of a dry formulation containing antigen and adjuvant to skin of the animal or human. The dry formulation may be a powder or a unit-dose patch. Use of adjuvant is not required if the antigen is sufficiently antigenic. Transcutaneous immunization may be induced with or without penetration enhancement.

The invention provides novel recombinant immunotoxins comprising domain III of cholix toxin and exotoxin from Vibrio cholerae. The present invention further provides methods for using the compositions of the present invention to (i) induce apoptosis in a cell bearing one or more surface markers (ii) inhibit unwanted growth, hyperproliferation or survival of a cell bearing one or more cell surface markers, (iii) treat a condition, such as a cancer, (iv) provide therapy for a mammal having developed antibodies to Pseudomonas exotoxin A, and (v) provide therapy for a mammal having developed a disease caused by the presence of cells bearing one or more cell surface marker.

The present invention relates to methods for preventing or treating head and neck squamous cell cancer and bladder cancer using an immunotoxin comprising (a) a ligand that binds to a protein on the cancer cell attached to; (b) a toxin that is cytotoxic to the cancer cell. In a specific embodiment, the invention is directed to the prevention or treatment of head and neck squamous cell cancer or bladder cancer using VB4-845, which is a recombinant immunotoxin comprising a humanized, MOC31-derived, single-chain antibody fragment that is fused to a truncated form of Pseudomonas exotoxin A. Also encompassed by the invention are combination therapy methods, including the use of reduced dosages of chemotherapeutic agents, for the prevention or treatment of cancer. Also encompassed by the invention are formulations and methods for direct administration of the recombinant immunotoxin to the carcinoma, for the prevention or treatment of cancer.

Methods and compositions for inhibiting the production of exotoxins are disclosed. The compositions include an effective amount of an isoprenoid inhibitory compound to substantially inhibit the production of exotoxins by Gram positive bacteria.

A method and apparatus for preventing and treating septicemia in patient blood is provided. The extracorporeal system includes an antimicrobial device to inactivate at least 99% of bloodborne microorganisms, a hemoconcentrator / filtration unit to remove approximately 50-75% of target molecules from the patient blood and a filter unit to remove target molecules from patient blood from the sieved plasma filtrate. Target molecules are produced by microorganisms, as well as by the patient's cells. These molecules include endotoxins from Gram negative bacteria, exotoxins from Gram negative and Gram positive bacteria, as well as RAP protein mediator from Staphylococcus aureus, and cell mediators such as tumor necrosis factor-alpha, and interleukin 1-beta, interleukin 6, complement proteins C3a and C5a, and bradykinin.

The invention provides mutated, cytotoxic forms of Pseudomonas exotoxin A (PE) comprising a furin cleavage sequence conjugated or fused directly to residues 395-613 of PE or variants of that sequence. These minimal forms of PE are smaller than previous cytotoxic forms of PE, reduce non-specific toxicity, and reduce immunogenicity due to domain II or domain Ib of PE. The invention further provides nucleic acids encoding said PEs, chimeric molecules containing them, and methods of use thereof.

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 invention relates to methods for protecting and / or treating a mammal at risk of acquiring a condition associated with bacteria that produce a calmodulin exotoxin, a metalloproteinase exotoxin, or both, by administering a non-antibacterial tetracycline formulation.

Fusion antigen used as vaccine. The invention relates to a fusion antigen specific for a target cell. The fusion antigen contains a ligand moiety, a Pseudomonas exotoxin A translocation domain II, an antigenic moiety, and a carboxyl terminal moiety. The ligand moiety is capable of reacting, recognizing or binding to receptors on the target cell. The carboxyl terminal moiety permits retention and processing of the fusion antigen in the endoplasmic reticulum (ER) membrane of the target cell. Pharmaceutical compositions and methods of inducing an immune response using the same are also disclosed.

Methods and compositions relating to anti-CD22 antibodies with high binding affinity, and immunoconjugates comprising the anti-CD22 antibody linked to a therapeutic agent such as a Pseudomonas exotoxin or a detectable label. The invention provides diagnostic methods, and means to inhibit the growth of malignant B cells.

The present invention relates to methods for preventing or treating head and neck squamous cell cancer and bladder cancer using an immunotoxin comprising (a) a ligand that binds to a protein on the cancer cell attached to; (b) a toxin that is cytotoxic to the cancer cell. In a specific embodiment, the invention is directed to the prevention or treatment of head and neck squamous cell cancer or bladder cancer using VB4-845, which is a recombinant immunotoxin comprising a humanized, MOC31-derived, single-chain antibody fragment that is fused to a truncated form of Pseudomonas exotoxin A. Also encompassed by the invention are combination therapy methods, including the use of reduced dosages of chemotherapeutic agents, for the prevention or treatment of cancer. Also encompassed by the invention are formulations and methods for direct administration of the recombinant immunotoxin to the carcinoma, for the prevention or treatment of cancer.

The invention provides mutated, cytotoxic forms of Pseudomonas exotoxin A (PE) comprising a furin cleavage sequence conjugated or fused directly to residues 395-613 of PE or variants of that sequence. These minimal forms of PE are smaller than previous cytotoxic forms of PE, reduce non-specific toxicity, and reduce immunogenicity due to domain II or domain Ib of PE. The invention further provides nucleic acids encoding said PEs, chimeric molecules containing them, and methods of use thereof.

The invention provides chimeric proteins comprising a non-toxic Pseudomonas exotoxin A sequence and a Type IV pilin loop sequence, wherein the Type IV loop sequence is inserted within the non-toxic Pseudomonas exotoxin A. The invention also provides polynucleotides encoding the chimeric proteins, and compositions comprising the polynucleotides or the chimeric proteins. The invention also provides methods for using the chimeric proteins, polynucleotides and compositions of the invention.

Nucleic acids encoding a chimeric or fusion polypeptide which polypeptide comprises a first domain comprising a translocation polypeptide; and a second domain comprising at least one antigenic peptide are disclosed. The preferred translocation polypeptide is a bacterial toxin translocation polypeptide, such as domain II of Pseudomonas aeruginosa exotoxin A (ETA(dII)). Such nucleic acids, expression vectors thereof, and cells expressing these vectors are used as vaccine compositions in a method for enhancing an antigen specific immune response, a method of increasing the numbers of CD8+ CTLs specific for a selected desired antigen in a subject, or a method of inhibiting the growth of a tumor in a subject.

A reagent is provided for the detection of an exotoxin protein produced by a betahemolytic streptococcus bacteria suspected of being present in a host biological fluid collected from a subject. A kit is provided that is readily usable by an unskilled user and merely requires that an element of the kit be contacted with a biological sample and that element is then subjected to electromagnetic spectral energy. The incident electromagnetic spectral energy then reacts with the exotoxin protein indicator and can be reliably measured by an electromagnetic spectral emission. The emission is measured by a reporting module and is displayed to the user in a form recognized by the user's sensory systems; sight, sound, etc. or a combination thereof.

Disclosed are methods and compositions for the inhibition of modulation of T cell costimulatory pathway by a pathogenic agent, particularly, the inhibition of activation of a T cell costimulatory pathway, preferably, the CD28 / B7 pathway, by a pyrogenic exotoxin. The method of the invention is based on the inhibition of the direct interaction of a superantigen with a specific site within the dimer interface of a CD28 family member, using immunomodulatory peptides. Further disclosed are specific antagonist immunomodulatory peptides comprising an amino acid sequence derived from a dimer interface of a T cell co-stimulatory pathway member, or peptides which comprise an amino acid sequence which specifically binds to an amino acid sequence within the dimer interface of a T cell co-stimulatory pathway member. Compositions comprising said peptides and methods for the treatment of immune-related disorders are also disclosed. Also disclosed is the use of the CD28 molecule or any fragment thereof comprising the sAg binding site in a method of screening for a test substance which specifically binds to the CD28 molecule and is capable of antagonizing pyrogenic exotoxin-mediated activation of Th1 lymphocytes.

Fusion antigen used as vaccine. The invention relates to a fusion antigen specific for a target cell. The fusion antigen contains a ligand moiety, a Pseudomonas exotoxin A translocation domain II, an antigenic moiety, and a carboxyl terminal moiety. The ligand moiety is capable of reacting, recognizing or binding to receptors on the target cell. The carboxyl terminal moiety permits retention and processing of the fusion antigen in the endoplasmic reticulum (ER) membrane of the target cell. Pharmaceutical compositions and methods of inducing an immune response using the same are also disclosed.

The present invention provides a PRRSV subunit vaccine comprising a fusion protein having neutralization titers evoked, PE-PQGAB-K3, which comprises a chimeric polypeptide containing N-terminal portions of PRRSV ORF5 and ORF6 structure proteins; a portion of Pseudomonas exotoxin A binding and translocation domain; and a carboxyl terminal domain containing KDEL-KDEL-KDEL(K3) sequence. Less inflammation of PE-PQGAB-K3 vaccine group in their lungs post being PRRSV-challenged indicates that PQGAB without an antigen-specific allergy effect. Importantly, PE-PQGAB-K3 vaccine presents a good protection against PRRSV infection than control groups in pig challenged experiment.

This invention provides Pseudomonas exotoxin A-like chimeric immunogens that include a non-native epitope in the Ib domain of Pseudomonas exotoxin. Methods of eliciting an immune response using these immunogens also are provided.

The invention relates to a pseudomonas aeruginosa mutant strain genetic engineering mutant strain, in particular to a pseudomonas aeruginosa mutant strain exotoxin A attenuated strain, and further relates to a preparation method of the mutant strain and application of the mutant strain or the attenuated strain in preparing vaccines or adjuvant therapy drugs.

The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and / or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.

The present invention provides a modified toxin having an ETA moiety that has the furin site replaced with a cancer-associated protease site. The present invention also provides modified immunotoxins having a ligand that binds to a cancer cell attached to an ETA moiety that has the furin site replaced with a cancer-associated protease site. Also provided are a method of inhibiting or destroying mammalian cancer cells using the immunotoxins of the invention and pharmaceutical compositions for treating human cancer.