36 results about "Recombinant immunotoxin" patented technology

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 of B cells and B cell malignancies 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 leukemia and lymphoma cells.

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 of B cells and B cell malignancies 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 leukemia and lymphoma cells.

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 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.

We tested the in vitro and in vivo efficacy of a recombinant bispecific immunotoxin that recognizes both EGFRwt and tumor-specific EGFRvIII receptors. A single chain antibody was cloned from a hybridoma and fused to toxin, carrying a C-terminal peptide which increases retention within cells. The binding affinity and specificity of the recombinant bispecific immunotoxin for the EGFRwt and the EGFRvIII proteins was measured. In vitro cytotoxicity was measured. In vivo activity of the recombinant bispecific immunotoxin was evaluated in subcutaneous models and compared to that of an established monospecific immunotoxin. In our preclinical studies, the bispecific recombinant immunotoxin, exhibited significant potential for treating brain tumors.

Recombinant immunotoxins containing a cytotoxic RNAse fused to an antibody or antibody fragment may be produced in mammalian cell culture. Surprisingly, immunotoxins containing a cytotoxic RNAse fused to the N-terminus of one antibody variable domain can be prepared and retain the ability to specifically bind antigen. The immunotoxins may be used in a variety of therapeutic methods for treating diseases or syndromes associated with unwanted or inappropriate cell proliferation or activation.

The present invention relates to novel antibodies, antibody fragments and antibody conjugates and single-chain immunotoxins reactive with human carcinoma cells. More particularly, the antibodies, conjugates and single-chain immunotoxins of the invention include: a murine monoclonal antibody, BR96; a human / murine chimeric antibody, ChiBR96; a F(ab′)2 fragment of BR96; ChiBR96-PE, ChiBR96-LysPE40, ChiBR96 F(ab′)2-LysPE40 and ChiBR96 Fab′-LysPE40 conjugates and recombinant BR96 sFv-PE40 immunotoxin. These molecules are reactive with a cell membrane antigen on the surface of human carcinomas. The BR96 antibody and its functional equivalents, displays a high degree of selectivity for carcinoma cells and possess the ability to mediate antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity. In addition, the antibodies of the invention internalize within the carcinoma cells to which they bind and are therefore particularly useful for therapeutic applications, for example, as the antibody component of antibody-drug or antibody-toxin conjugates. The antibodies also have a unique feature in that they are cytotoxic when used in the unmodified form, at specified concentrations.

The invention belongs to the biotechnology field, in particular to recombination immunotoxin of anti-EGFR single-chain antibody fusion Gelonin, a preparation method thereof and the usage thereof. Thetechnical problem to be solved is to provide recombination immunotoxin taking an epidermal growth factor receptor as a target. The recombination immunotoxin is formed by the single-chain antibody of the EGFR and toxin-protein Gelonin fusion expression. The technical solution plays a role in the specific cytocidal effect on tumor by using the targeting ability of the single-chain antibody on the EGFR high- expression tumor and the cytotoxic effect of Gelonin and has obvious effect; the preparation method is simple and convenient, has good application prospect, and provides a new choice for thetreatment of the tumor.

The new-type recombinant immunotoxin plasmid for activated Th1 cell is prepared with chemotactic factor Rantes as targeting molecule and the active segment DT390 of diphtheria toxin as toxin molecule and through gene recombination. The preparation process of the immunotoxin plasmid includes the construction of the recombinant plasmid, the preparation of the recombinant transinfected engineering bacterium and other steps. The immunotoxin plasmid has strict targeting property and can attack activated Th1 cell with DT390 specificity by means of the targeting of Rantes to induce specific immune tolerance while avoiding non-selective killing all the T cell. The present invention is especially suitable for preventing and treating autoimmune disease and organ transplantation rejection, and may be also used for treating some tumors.

The invention discloses a mesenchymal stem cell preparation capable of secreting specific recombinant immunotoxin Gas6-PE38KDEL for targeted therapy of malignant melanoma. A new therapy direction is provided for targeted therapy of the malignant melanoma. According to the mesenchymal stem cell preparation disclosed by the invention, a specific immunotoxin Gas6-PE38KDEL adenovirus vector composed of Axl ligand (Gas6) and a pseudomonas aeruginosa exotoxin derivative PE38KDEL is firstly constructed; a mesenchymal stem cell is infected in vitro; and the Gas6-PE38KDEL secreted by infected mesenchymal stem cell can be applied to specific targeted killing of malignant melanoma cells. The invention further provides a preparation method of the mesenchymal stem cell preparation.

The invention belongs to the biotechnology field, in particular to recombination immunotoxin of anti-EGFR single-chain antibody fusion Gelonin, a preparation method thereof and the usage thereof. The technical problem to be solved is to provide recombination immunotoxin taking an epidermal growth factor receptor as a target. The recombination immunotoxin is formed by the single-chain antibody of the EGFR and toxin-protein Gelonin fusion expression. The technical solution plays a role in the specific cytocidal effect on tumor by using the targeting ability of the single-chain antibody on the EGFR high- expression tumor and the cytotoxic effect of Gelonin and has obvious effect; the preparation method is simple and convenient, has good application prospect, and provides a new choice for thetreatment of the tumor.

Mesothelin is a differentiation antigen present on the surface of ovarian cancers, mesotheliomas and several other types of human cancers. Because among normal tissues, mesothelin is only present on mesothelial cells, it represents a good target for antibody mediated delivery of cytotoxic agents. The present invention is directed to improved recombinant immunotoxins comprising anti-mesothelin antibodies, including Fv molecules with particularly high affinity for mesothelin, and a Pseudomonas Exotoxin moiety which has been modified to reduce its immunogenicity and protease sensitivity and providing a better cytotoxicity for cells which express mesothelin. The RITs are well-suited for the treatment of cancers of the ovary, stomach, squamous cells, mesotheliomas and other malignant cells expressing mesothelin.

The high efficiency expression plasmid of recombinant immune toxin IP10-DT390 constituted by means of gene engineering technology is for activated Th1 cell specifically. After transfected into body, the immune toxin plasmid expresses high specific recombinant immune toxin with IP10 as targeting molecule, active diphtherin segment DT390 as toxin molecule and the specific membrane acceptor CXCR3 of activated Th1 cell as the target point. The preparation process of the immune toxin plasmid includes the constitution of recombinant plasmid, the preparation of recombinant plasmid transfected engineering bacterium and other steps. The plasmid expressed recombinant immune toxin has strict targeting property of attacking activated Th1 cell specifically by means of targeting IP10 to induce specific immunity tolerance and avoid killing normal T cells, and is especially suitable for preventing and treating of autoimmune disease and organ transplantation rejection, and some tumors.

The invention discloses recombinant humanized immunotoxin Gigantoxin-4-4D5scFv. The immunotoxin contains anti human epidermal growth factor receptor-2 (HER-2) single-chain antibody 4D5scFv and sea anemone cytolysin Gigantoxin-4 and is formed through fusing and expression of HER-2 and sea anemone cytolysin Gigantoxin-4. Targeting of the single-chain antibody at a HER-2 high-expression tumor and the splitting effect of Gigantoxin-4 on cytomembrane are used, so that a specific killing effect on the tumor is achieved. The immunotoxin has a strict targeting property, and damage to normal cells is avoided; the effect of tumor killing can be achieved without cell internalization and transferring; drug resistance cannot be produced easily; a preparation method is simple, and the antitumous effect is obvious. The immunotoxin has a good application prospect and can be used for treating high-expression HER-2 tumor cells.

The present invention relates to new recombinant humanized immunotoxin hS83-P34, which contains fusion protein comprising the antigen associated molecule of humanized cytotoxic T cell antigen 4 and human porforin channel forming active molecule. The immunotoxin of the present invention has strict targeting, less tendency of damaging health cell, less toxic side effect, no need of internalization and intracellular transport, high acting efficiency, less likelihood of generating corresponding antibody, weak immunogenicity and less tendency of generating drug resistance. It may be used in treating some tumors and autoimmune diseases and suppressing immunologic rejection reaction in organ transplantation.

A single-chain antibody resisting HIV-1 outer membrane protein and two recombinant immunotoxins resisting HIV-1 are disclosed. Said single-chain antibody has particular gene sequence and can be used for the diagnosis and immunotherapy of HIV infection. Said recombinant immunotoxins is prepared by using said single-chain antibody to respectively replace the receptor binding regions of pseudomonas aeruginosa exotoxin and diphtherin, and can be used as the medicine to treat HIV infection.

A new type of recombinant immunotoxin plasmid for activating Th1 cells, with the chemokine Rantes as the guiding molecule and the active fragment DT390 of diphtheria toxin as the toxin molecule, constructed by gene recombination. The preparation method of the immunotoxin plasmid comprises the steps of constructing the recombinant plasmid, preparing engineering bacteria transfected by the recombinant plasmid, and the like. The immunotoxin plasmid has strict targeting, and can specifically attack activated Th1 cells with DT390 through the guidance of Rantes, and induce specific immune tolerance, thereby avoiding non-selective killing of all T cells. It is especially suitable for the prevention and treatment of autoimmune diseases and organ transplantation rejection, and can also be applied to the treatment of certain tumors.