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 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 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.