85 results about "Integrin binding" patented technology

The present invention is in the fields of cell biology, immunology and oncology. The invention provides humanized antibodies that recognize α_vβ₆ integrins, which antibodies comprise a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also provides methods for preparation of such antibodies, pharmaceutical compositions comprising them, and methods of treating, diagnosing and/or preventing various diseases and disorders by administering the humanized anti-α_vβ₆ antibodies of the invention. The invention also relates to the identification of differential expression of the integrin α_vβ₆ on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin α_vβ₆.

Disclosed are peptides having a cystine knot structural motif and comprising a sequence engineered for specificity against α_IIbβ₃ integrin, found on platelets, and a method of using the same in anti-thrombotic therapies. The present peptides utilize a cystine knot scaffold derived from modified agouti-related protein or agatoxin, An alternate library screening strategy was used to isolate variants of peptides that selectively bound to α_IIbβ₃ integrin or to both α_IIbβ₃ and α_Vβ₃ integrins. Unique consensus sequences were identified within the identified peptides suggesting alternative molecular recognition events that dictate different integrin binding specificities. In addition, the engineered peptides prevented human platelet aggregation in a plasma-based assay and showed high binding affinity for α_IIbβ₃ integrin.

Contortrostatin, a homodimeric disintegrin, modulates the adhesion, motility, and invasiveness of integrin expressing tumor cells. When formulated as a pharmaceutically acceptable composition, the proteins can be used to treat patients by inhibiting or disrupting disease processes associated with an integrin binding to an αvβ3 or αvβ5 integrin.

A method of enhancing binding of cells to an integrin-binding ligand comprises treating integrin-expressing cells in vitro with an agonist of integrin, wherein the integrin is selected from the group consisting of α4β1, α5β1, α4β7, αvβ3 and αLβ2, and contacting the treated cells with an integrin-binding ligand; integrin agonist compounds having the general formula I; methods of treating integrin-expressing cells with such agonists to enhance binding; and therapeutic methods comprising administering agonist-treated cells or agonist compounds to a mammal.

The present invention concerns fragments and variants of the HYD1 peptide; polynucleotides encoding the peptides; host cells genetically modified with the polynucleotides; vectors comprising the polynucleotides; compositions containing these peptides, polynucleotides, vectors, or host cells; and methods of using the peptides, polynucleotides, vectors, and host cells as inhibitors of aberrant cell growth in vitro or in vivo, e.g., as anti-cancer agents for treatment of cancer, such as myeloma. The present invention further includes a method of increasing the efficacy of chemotherapy and radiation therapy, comprising administering an agent that binds β1 integrin to a patient in need thereof. In one embodiment, the β1 integrin binding agent is the HYD1 peptide, or a functional fragment or variant thereof. In another aspect, the invention pertains to a composition (an adhesion trap) comprising a substrate (also referred to as a surface or support) with a HYD1 peptide, or fragment or variant thereof, immobilized to the substrate, and a method of removing circulating tumor cells (CTC) from blood by contacting a subject's blood with the immobilized peptide. Another aspect of the invention concerns a method of identifying modulators of peptide binding. Another aspect of the invention concerns a method for detecting CTC.

The invention provides a method of inducing an immune response in a mammal. The method comprises administering to the mammal an adenoviral vector comprising (a) a subgroup C fiber protein wherein a native coxsackievirus and adenovirus receptor (CAR)-binding site is disrupted, (b) a subgroup C penton base protein wherein a native integrin-binding site is disrupted, and (c) a nucleic acid sequence encoding at least one antigen derived from an infectious agent other than an adenovirus which is expressed in the mammal to induce an immune response.

The present invention provides recombinant triple helical proteins or collagen-like proteins comprising a prokaryotic protein or one or more domains of a prokaryotic protein comprising a collagen-like peptide sequence of repeated Gly-Xaa-Yaa triplets and, optionally, one or more domains from a mammalian collagen. Also provided are expression vectors and host cells containing the expression vectors to produce these recombinant proteins and methods of production for the same. Additionally, antibodies are provided that are directed against a recombinant collagen-like protein that, preferably, binds an integrin. Furthermore, a method of screening for potential therapeutic compounds that inhibit the integrin-binding or -interacting activities of recombinant collagen-like proteins.

The present invention provides recombinant triple helical proteins or collagen-like proteins comprising a prokaryotic protein or one or more domains of a prokaryotic protein comprising a collagen-like peptide sequence of repeated Gly-Xaa-Yaa triplets and, optionally, one or more domains from a mammalian collagen. Also provided are expression vectors and host cells containing the expression vectors to produce these recombinant proteins and methods of production for the same. Additionally, antibodies are provided that are directed against a recombinant collagen-like protein that, preferably, binds an integrin. Furthermore, a method of screening for potential therapeutic compounds that inhibit the integrin-binding or -interacting activities of recombinant collagen-like proteins.

Novel peptides that are capable of binding to uPAR and inhibiting the binding of an integrin and vitronectin are described. Also provided are nucleic acid sequences encoding the novel peptides. Methods for screening for small molecules, other peptides, or peptoids that mimic the antagonistic function of the peptides of the invention are described. The invention has applications in design of therapeutics for treating disorders characterized by upregulation of uPA and uPAR, and cancer and chronic inflammation, cell migration or uPAR: integrin binding interactions, and diagnostical applications to such disorders.

The present invention provides a method of treating cancer with an integrin-binding-Fc fusion protein alone or in combination with IL-2 and/or an immune stimulant (i.e., an immune checkpoint stimulator), and/or an immune checkpoint inhibitor. The invention also provides composition for use in such methods.

The present invention provides recombinant triple helical proteins or collagen-like proteins comprising a prokaryotic protein or one or more domains of a prokaryotic protein comprising a collagen-like peptide sequence of repeated Gly-Xaa-Yaa triplets and, optionally, one or more domains from a mammalian collagen. Also provided are expression vectors and host cells containing the expression vectors to produce these recombinant proteins and methods of production for the same. Additionally, antibodies are provided that are directed against a recombinant collagen-like protein that, preferably, binds an integrin. Furthermore, a method of screening for potential therapeutic compounds that inhibit the integrin-binding or -interacting activities of recombinant collagen-like proteins.

Dental products such as toothpastes, mouthwash and dental floss are disclosed which products are enhanced by having dissolved, dispersed or coated thereon a compound which promoted bone growth. Preferred compounds are peptide sequences comprising 10 to 50 amino acids are disclosed. The sequences are characterized by containing an integrin binding motif such as RGD sequence and the remainder of amino acids contiguous with the RGD sequence in matrix extracellular phosphoglycoprotein. The sequences may be formulated for dispersed in toothpaste or a mouthwash and administered to enhance bone/tooth growth. When the dental products are used repeatedly over time they enhance good dental health.

The invention relates to a method for inhibiting an adam protease, comprising inhibiting binding to an integrin-binding loop of a disintegrin domain in the adam protease. Also provided are cyclic peptides which inhibit binding to an integrin-binding loop of an adam protease, as well as associated pharmaceutical compositions, uses and methods of treatment.

Disclosed are knottin peptides containing non-natural amino acids so that they can be formed by chemical conjugation into two or more knottin monomers. The knottin monomers comprise a non-natural amino acid such as an aminooxy residue within the polypeptide sequence. The exemplified dimers were produced by oxime formation between two aldehyde groups present on a polyether linker and an aminooxy functional group that was site-specifically incorporated the knottin. Knottins variants based on EETI (Ecballium elaterium trypsin inhibitor) and AgRP (Agouti-related protein) were engineered to contain integrin-binding loops. These dimers were shown to have increased binding strength to integrins on U87MG tumor cells, achieving significant increases in inhibition of cell adhesion and proliferation. Also disclosed are knottin monomers comprising an aminooxy residue; these may be conjugated to molecules such as doxorubicin.

The present invention provides a cyclic peptide comprising three colinear amino acids, arginine-lysine-lysine (RKK) for binding to integrin α2I domain. Potent inhibitor of laminin-1 interaction. The invention also provides methods of using these peptides to block integrin function and inhibit cell migration.

Media compositions and methods of enhancing binding of cells to an integrin-binding ligand comprising treating integrin-expressing hematopoietic stem cells ex vivo with an agonist of integrin, wherein the integrin is selected from the group consisting of α4β1, α5β1, α4β7, αvβ3 and αLβ2, and contacting the treated cells ex vivo with an integrin-binding ligand; integrin agonist compounds having the general formula I; methods of treating integrin-expressing cells with such agonists to enhance binding; and therapeutic methods comprising administering agonist-treated cells with minimal exposure agonist compounds to a mammal requiring stem cell transplantation in the management of hematologic cancers and genetic diseases.

The invention relates to the new applications of integrin beta 4 binding protein (ITGB4BP) and derivates thereof, or gene recombinant expression vector expressing the ITGB4BP or derivates thereof in preventing and/or treating hypertrophic scar or fibrosis lesion; wherein, the amino acid sequence of the ITGB4GB is SEQ ID NO 1; the derivates of the ITGB4BP are protein derivates retaining the combining site and the functional site of the ITGB4BP (SEQ ID NO 1). The application is realized by applying the ITGB4BP or derivates thereof, or gene recombinant expression vector expressing the ITGB4BP orderivates thereof, or the drug combination or the kit of the invention on subjects with an effective dose in treatment. The drug combination or the kit contains the ITGB4BP or derivates thereof, or gene recombinant expression vector expressing the ITGB4BP or derivates thereof and an officinal excipient or vectors and the like with an effective dose in treatment. Preferably, the subjects are humanbeings or animals.

The present invention provides alternative in vivo imaging agents suitable for use in the detection of α_vβ₆ expressed in a subject. The invention also provides a method for obtaining said in vivo imaging agents, and use of the in vivo imaging agents in determining α_vβ₆ expressed in a subject.