24results about "Integrin superfamily" patented technology

Described herein are muscle-specific targeting moieties and compositions including the muscle specific targeting motifs. Also described herein are uses of the muscle-specific targeting motifs and compositions including the muscle specific targeting moieties. In some embodiments, the muscle-specific targeting moieties and compositions including the muscle specific targeting moieties can be used to direct delivery of a cargo to a muscle cell.

The invention provides a DC-activated chimeric antigen receptor, a vector, a gene engineering modified cell, a drug, a preparation method and application, and particularly belongs to the technical field of biological medicine. The DC activated chimeric antigen receptor sequentially comprises a signal peptide, an antigen binding structural domain, a hinge region, a transmembrane structural domain and an intracellular signal activation structural domain, the intracellular signal activation structural domain comprises one or more than two of TAC1, BAFFR, LRP1, OX40L, FcR gamma, DC-SIGN, TLR4, 4-1BB, CD40, CD86, DAP12, B7-H3, CD49a, BLAME, SLAMF4, MARCO, TLR7, CD103, CD54 and CD83. The invention further discloses a preparation method of the intracellular signal activation structural domain. The DC activated chimeric antigen receptor disclosed by the invention can enhance a DC activation signal, overcome microenvironment inhibition of solid tumors and realize immunotherapy of the solid tumors.

The present invention provides methods for preselecting TILs based on PD-1, CD39, CD38, CD103, CD101, LAG3, TIM3, and / or TIGIT expression, as well as methods for expanding those preselected PD-1, CD39, CD38, CD103, CD101, LAG3, TIM3, and / or TIGIT positive TILs to produce therapeutic TIL populations with enhanced tumor-specific killing capacity (e.g., enhanced cytotoxicity).

A composition is provided comprising a first polypeptide comprising a first fragment or analog or derivative of the extracellular domain of ITGA2B or ITGB3 and a dimerization domain, and a second polypeptide comprising a second fragment or analog or derivative of the extracellular domain of ITGA2B or ITGB3 and a dimerization domain. Polypeptides comprising fragments of the extracellular domain of ITGA2B or ITGB3 are also provided. Pharmaceutical compositions comprising the composition, polypeptide, nucleic acid system, and molecule encoding the polypeptide of the above composition are also provided, as well as therapeutic methods using the above composition or polypeptide, methods for determining suitability for therapeutic use of the above composition or polypeptide, and methods for producing the above composition or protein.

The present disclosure relates to an engineered hematopoietic cell comprising a very late antigen-4 (VLA-4) variant and uses thereof in treating an inherited genetic disorder or an acquired disorder.

Provided herein are recombinant minipigs that do not express endogenous porcine CD47 and SIRPA, but express human or humanized CD47 and human or humanized SIRPA under the same regulatory elements as the endogenous porcine CD47 and SIRPA. Also provided are cells, tissues, and organs derived from such recombinant minipigs. Additionally provided herein are methods of transplanting grafts derived from such recombinant minipigs of a first donor with or without bone marrow derived from such recombinant minipigs of a second donor.

Provided herein are α4β 1 / 7 Integrin receptor ligand-containing compounds, methods of delivering the compounds, and methods of using the compounds to treat diseases, disorders, and conditions in a subject (e.g., diseases, disorders, and conditions of the central nervous system). 1 / 7 The present invention relates to compounds (eg, any of those defined herein) and methods for targeting cells expressing integrin receptors (collectively referred to as "integrin receptors").

Compounds having affinity for integrins, the synthesis of these compounds, and the use of these compounds as ligands to facilitate the delivery of cargo molecules to cells expressing integrins are described. The described integrin targeting ligands have serum stability and affinity for αvβ3 integrin and / or αvβ5 integrin, and are suitable for conjugation to cargo molecules, such as such as oligonucleotide-based therapeutic agents (e.g., RNAi agents), to facilitate delivery of the cargo molecules to cells and tissues, such as tumor cells, that express integrin αvβ3, integrin αvβ5, or both integrin αvβ3 and integrin αvβ5. Compositions that include integrin targeting ligands and methods of use are also described.

The present disclosure provides an antibody fusion protein comprising: (i) a heavy chain comprising a variable region sequence comprising the amino acid sequence of SEQ ID NO: 1; and (ii) a light chain comprising a variable region sequence comprising the amino acid sequence of SEQ ID NO: 8, wherein the light chain is fused at its C-terminus to an A1-A2 domain comprising the amino acid sequence of SEQ ID NO: 11. Nucleic acids encoding all or a portion of the antibody fusion protein are provided, as well as methods of using the antibody fusion protein, e.g., in treating CD20-positive cancers. The present disclosure further provides mutant A1-A2 domain peptides.

Provided herein are recombinant miniature swine without expression of endogenous porcine CD47 and SIRPA, but with the expression of human or humanized CD47 and human or humanized SIRPA under the same regulatory elements as the endogenous porcine CD47 and SIRPA. Also provided are cells, tissues, and organs derived from such recombinant miniature swine. Furthermore, provided herein are methods of transplanting a graft from a first donor of such recombinant miniature swine with or without bone marrow from a second donor of such recombinant miniature swine.

The present disclosure provides peptides that inhibit the binding interaction between beta integrins and G protein subunits and compositions, e.g., pharmaceutical compositions, particularly nanoparticle compositions, comprising the peptides, and methods of using the peptides to treat atherosclerosis, thrombosis, stroke, heart attack, inflammation, acute respiratory distress syndrome (ARDS), autoimmune disease, hemodialysis AV fistula, or organ transplantation.

To provide pharmaceutical compositions for the diagnosis, prevention, and / or treatment of age-related cognitive decline, including pathological neurodegeneration. [Solution] A pharmaceutical composition comprising the following components: a therapeutically effective amount of one or more of the following: a CD103 inhibitor, a perforin 1 inhibitor, and an IFNγ inhibitor, wherein the CD103 inhibitor is an anti-CD103 antibody, selected from the group consisting of PE anti-human CD103 antibody derived from clone Ber-ACT8, mouse anti-human CD103 monoclonal antibody (mAb) derived from clone 2G5.1, humanized antibody of 2G5.1, OX-62, humanized antibody of OX-62, anti-mouse CD103 mAb derived from clone 2E7, humanized antibody of 2E7, and paxilin; the perforin 1 inhibitor is selected from the group consisting of diarylthiophene and GSK2126458; and the IFNγ inhibitor is selected from the group consisting of mesopram and locagramide.

A non-toxic anti-angiogenesis protein that inhibits tumor growth and exhibits in vitro activity in induction of angiogenic endothelial cell apoptosis without targeting VEGF / VEGFR or any other RTK pathways is described. The protein targets integrins αvβ3, at a groove in the βA domain of β3 formed by α2 helix, B-C loop, and α2-α3 loop.

The present invention provides a composition for the diagnosis, prevention, and / or treatment of age-related cognitive decline, including pathological neurodegeneration, as well as diagnostic, preventive, and / or therapeutic methods using the composition. [Solution] Provided are methods and systems for diagnosing, preventing, and treating one or both of age-related neurodegeneration and cognitive disorders. Provided are methods for protecting at-risk elderly subjects, subjects with mild cognitive impairment, and / or subjects with pathological neurodegeneration from cognitive decline and / or reducing the severity of such decline, comprising administering a CD103 inhibitor, which is an inhibitor of an effector molecule of CD8+ resident memory T cells, and / or a tolerogenic vaccine. Provided are methods for identifying subjects susceptible to or experiencing age-related neurodegeneration, comprising detecting elevated levels of CD103+ resident memory T cells. Provided are kits for collecting and quantifying CD103+CD8+ resident memory T cells.

The present invention relates to biologics that inhibit angiogenesis. In particular, the present invention relates to fusion proteins that inhibit the integrin activation pathway and one other angiogenic factor activation pathway, as well as pharmaceutical compositions of such fusion proteins and methods of making and using the same.

In general, the present disclosure provides novel bacterial translocation domains for use in cellular delivery. One example is a translocation domain having the amino acid sequence of SEQ ID NO:3, from the Austwickia chelonae protein of SEQ ID NO:2. Translocase domains from other bacterial strains and species are also described (e.g., SEQ ID NOs:4-17 and 36-48). Recombinant polypeptides comprising those translocation domains are described. The recombinant polypeptides are intended for use in delivery of cargo molecules, including therapeutic polypeptides that can be used in the treatment of disease.

Provided herein are anti-avb6 integrin engineered polypeptides, fusion proteins thereof with an Fc domain, and pharmaceutically acceptable compositions comprising the same. The anti-avb6 integrin engineered polypeptides of the present technology selectively bind the avb6 integrin with low-nanomolar or picomolar binding activity.

The present invention relates to cells containing a chimeric costimulatory antigen receptor (CoStAR) useful in adoptive cell therapy (ACT). The present invention relates to cells containing a chimeric costimulatory antigen receptor (CoStAR), which is useful for adoptive cell therapy (ACT). CoStAR can act as a modulator of cellular activity to enhance responses to defined antigens. The present invention also provides the CoStAR protein, nucleic acids encoding CoStAR, and their therapeutic uses.

A non-toxic anti-angiogenesis protein that inhibits tumor growth and exhibits in vitro activity in induction of angiogenic endothelial cell apoptosis without targeting VEGF / VEGFR or any other RTK pathways is described. The protein targets integrins αvβ3, at a groove in the βA domain of β3 formed by α2 helix, B-C loop, and α2-α3 loop.

Provided are a tissue-specific promoter and use thereof. The tissue-specific promoter has a nucleic acid sequence comprising more than 80% of the sequence as shown in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4. The tissue-specific promoter can promote the specific expression of a coding gene in endothelial cells (ECs) or megakaryocyte-platelet cells and can be applied to gene therapy in which a gene is required to be specifically expressed in ECs or megakaryocyte-platelet cells, ensuring a therapeutic effect, reducing a risk of immune rejection and saving a therapeutic cost.

This disclosure provides a humanized anti-CD11b antibody and a method for using the same.

Compositions comprising a first polypeptide comprising a first fragment of an extracellular domain of ITGA2B or ITGB3 or an analog or derivative thereof and a dimerization domain and a second polypeptide comprising a second fragment of an extracellular domain of ITGA2B or ITGB3 or an analog or derivative thereof and a dimerization domain are provided. Polypeptides comprising fragments of an extracellular domain of ITGA2B or ITGB3 are also provided. Pharmaceutical compositions comprising the composition, polypeptide, nucleic acid systems and molecules encoding the polypeptides of the composition and invention and methods of treatment and determining suitability for treatment using the compositions or polypeptides; as well as methods of producing the compositions or proteins are also provided.

Provided are methods for determining whether a glioblastoma (GBM) tumor or GBM cancer cell will be sensitive to a treatment targeting the integrin avb3 (αvβ3) pathway, comprising determining whether the GBM tumor or the GBM cancer cell expresses both avb3+ and Glut3+ along with a specific genetic signature associated with Glut3 addiction, where in alternative embodiments a cell is Glut3 addiction if the GBM tumor or the GBM cancer cell has markers consistent with the Classical or the Proneural molecular subtypes of GBM, or, expresses markers consistent with a Glut3-addicted molecular signature, e.g., as listed in FIG. 11 or FIG. 23. Also provided herein are methods of treating glioblastoma (GBM) tumors found to be sensitive to agents targeting or inhibiting the integrin avb3 (αvβ3) pathway, wherein the sensitivity is determined by methods as provided herein.

Generally, the present disclosure provides novel bacterial translocation domains for use in cellular delivery. An example is the translocation domain from the Austwickia chelonae protein of SEQ ID NO:2, the translocation domain having the amino acid sequence of SEQ ID NO: 3. Translocase domains from other bacterial strains and species are also described (e.g. SEQ ID NOs: 4 to 17 and 36 to 48). Recombinant polypeptides comprising these translocation domains are described. The recombinant polypeptides are intended for use in delivery of cargo molecules, including therapeutic polypeptides that may be used to treat disease.