577results about "Polypeptide with fusion toxin" patented technology

Cysteine engineered anti-MUC16 antibodies are engineered by replacing one or more amino acids of a parent anti-MUC16 antibody with non cross-linked, reactive cysteine amino acids. Methods of design, preparation, screening, and selection of the cysteine engineered anti-MUC16 antibodies are provided. Cysteine engineered anti-MUC16 antibodies (Ab) are conjugated with one or more drug moieties (D) through a linker (L) to form cysteine engineered anti-MUC16 antibody-drug conjugates having Formula I:Ab-(L-D)p  Iwhere p is 1 to 4. Diagnostic and therapeutic uses for cysteine engineered antibody drug compounds and compositions are disclosed.

The present invention relates generally to methods and compositions for targeting the vasculature of solid tumors using immunological- and growth factor-based reagents. In particular aspects, antibodies carrying diagnostic or therapeutic agents are targeted to the vasculature of solid tumor masses through recognition of tumor vasculature-associated antigens, such as, for example, through endoglin binding, or through the specific induction of endothelial cell surface antigens on vascular endothelial cells in solid tumors.

This invention provides novel targeted antimicrobial compositions. In various embodiments chimeric moieties are provided comprising an antimicrobial peptide attached to a peptide targeting moiety that binds a bacterial strain or species.

The present invention provides methods for inhibiting interleukin-3 receptor-expressing cells, and, in particular, inhibiting the growth of such cells by using a diphtheria toxin-human interleukin-3 conjugate (DT-IL3) that is toxic to cells expressing the interleukin-3 receptor. In preferred embodiments, the DT-IL3 conjugate is a fusion protein comprising amino acids 1-388 of diphtheria toxin fused via a peptide linker to full-length, human interleukin-3. In certain embodiments, the methods of the present invention relate to the administration of a DT-IL3 conjugate to inhibit the growth of cancer cells and / or cancer stem cells in humans, which cells express one or more subunits of the interleukin-3 receptor. Exemplary cells include myeloid leukemia cancer stem cells. In other embodiments, the methods of the present invention relate to ex vivo purging of bone marrow or peripheral blood to remove cells that express one or more subunits of the interleukin-3 receptor such that the purged bone marrow or peripheral blood is suitable, e.g., for autologous stem cell transplantation to restore hematopoietic function.

A conjugate is disclosed herein, wherein the conjugate includes a ligand having the ability to specifically and stably bind to an external receptor or binding site on a tumor vasculature endothelial cell, wherein the external receptor or binding site is specific for tumor vasculature endothelial cells. The conjugate also includes an anticancer agent that is selectively toxic to cancer cells operatively attached to the ligand. The anticancer agent may be L-methioninase. Pharmaceutical compositions comprising the conjugate are also disclosed, as well as methods of treating a cancer tumor or cancer cells with a therapeutically effective amount of the conjugate.

Disclosed is a composition of matter of the formula(X1)a—(F1)d—(X2)b—(F2)e—(X3)c  (I)and multimers thereof, in which F1 and F2 are half-life extending moieties, and d and e are each independently 0 or 1, provided that at least one of d and e is 1; X1, X2, and X3 are each independently -(L)f-P-(L)g-, and f and g are each independently 0 or 1; P is a toxin peptide of no more than about 80 amino acid residues in length, comprising at least two intrapeptide disulfide bonds; L is an optional linker; and a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1. Linkage to the half-life extending moiety or moieties increases the in vivo half-life of the toxin peptide, which otherwise would be quickly degraded. A pharmaceutical composition comprises the composition and a pharmaceutically acceptable carrier. Also disclosed are a DNA encoding the inventive composition of matter, an expression vector comprising the DNA, and a host cell comprising the expression vector. Methods of treating an autoimmune disorder, such as, but not limited to, multiple sclerosis, type 1 diabetes, psoriasis, inflammatory bowel disease, contact-mediated dermatitis, rheumatoid arthritis, psoriatic arthritis, asthma, allergy, restinosis, systemic sclerosis, fibrosis, scleroderma, glomerulonephritis, Sjogren syndrome, inflammatory bone resorption, transplant rejection, graft-versus-host disease, and lupus and of preventing or mitigating a relapse of a symptom of multiple sclerosis are also disclosed.

Conjugates containing as a ligand a chemokine receptor targeting agents, such as chemokines, and a targeted agent, such as a toxin are provided. These conjugates are used to treat inflammatory responses associated with activation, proliferation and migration of immune effector cells, including leukocyte cell types, neutrophiles, macrophages, and eosinophils. The conjugates provided herein are used to lessen or inhibit these processes to prevent or at least lessen the resulting secondary effects. In particular, the conjugates are used to target toxins to receptors on secondary tissue damage-promoting cells. The ligand moiety can be selected to deliver the cell toxin to such secondary tissue damage-promoting cells as mononuclear phagocytes, leukocytes, natural killer cells, dendritic cells, and T and B lymphocytes, thereby suppressing the proliferation, migration, or physiological activity of such cells. Among preferred conjugates are fusion proteins having a chemokine, or a biologically active fragment thereof, as the ligand moiety linked to a cell toxin via a peptide linker of from 2 to about 60 amino acid residues.

Improved N-terminal capping modules for designed ankyrin repeat proteins (DARPins) conferring improved thermal stability to the DARPins are described, as well as nucleic acids encoding such proteins, pharmaceutical compositions comprising such proteins and the use of such proteins in the treatment of diseases.

The present invention uses co-expression of protease inhibitors and protease sensitive therapeutic agents that results in their localized production within the target tissue and inactivation outside of the target tissue, thereby increasing therapeutic activity and reducing the systemic toxicity. Inactivation is also accomplished by engineering protease degradation sites within the therapeutic construct for proteases, preferably those that are under-expressed within the target tissue yet present in non-target tissues within the body, resulting in therapeutic activity within the target tissue and inactivation outside of the target tissue. Novel chimeric proteins secreted by bacteria are also described. The chimeric proteins include chimeric toxins targeted to neoplastic cells and cells of the immune system. Novel combination therapies of these protease inhibitor:chimeric toxin-expressing bacteria together with small-molecule and biologic agents are also described. Non-conjugative bacteria capable of delivering phage / phagemids expression cassettes for DNA and RNA-based therapeutics are also described.

The present invention relates to combination therapies comprising at least one activator of Tie-2 and immunotherapies that target immune checkpoints. Combination therapies of the disclosure can provide therapeutic effects not obtained with singly-administered immunotherapies. Combination therapies can be used to increase the therapeutic efficacy of an immunotherapy, to provide lower dosages of an immunotherapy being administered, to lower a toxicity of an immunotherapy, or to manage a side effect of an immunotherapy.

The invention relates to mutant forms of lysenin. The invention also relates to analyte characterization using lysenin.