146 results about "Cell surface molecules" patented technology

The invention relates to a modified antibody which contains two or more H chain V regions and two or more L chain V regions of monoclonal antibody and can transduce a signal into cells by crosslinking a cell surface molecule(s) to thereby serve as an agonist. The modified antibody can be used as a signal transduction agonist and, therefore, useful as a preventive and / or remedy for various diseases such as cancer, inflammation, hormone disorders and blood diseases.

The invention relates to a modified antibody which contains two or more H chain V regions and two or more L chain V regions of monoclonal antibody and can transduce a signal into cells by crosslinking a cell surface molecule(s) to thereby serve as an agonist. The modified antibody can be used as a signal transduction agonist and, therefore, useful as a preventive and / or remedy for various diseases such as cancer, inflammation, hormone disorders and blood diseases.

This invention is directed to a soluble complex of ligands that binds to surface molecules of hemopoietic cells and result in their activation or expansion. The complex may be used in the activation and / or expansion of hemopoietic cells, optionally in combination with their transduction. The complex of ligands bind at least two cell surface molecules, such as one that plays a role in cell-cell adhesion and one that may or may not activate or stimulate the cell to promote growth and / or proliferation after binding to a ligand. A complex of ligands that bind two hemopoietic cell stimulatory molecules is also provided. The invention further provides for the use of the complex to target vectors to hemopoietic cells.

Novel cell surface molecules recognized by monoclonal antibodies against a cell surface molecule of lymphocytic cells that play an important role in autoimmune diseases and allergic diseases have been isolated, identified, and analyzed for their functions. The cell surface molecules are expressed specifically in thymocytes, lymphocytes activated by ConA-stimulation, and peripheral blood lymphocytes, and induce cell adhesion. Antibodies against the cell surface molecules significantly ameliorate pathological conditions of autoimmune diseases and allergic diseases.

Methods are provided for detecting formation of oligomeric complexes of molecules on the surface of cell membranes. These methods employ pairs of tagged probes and cleaving probes, each of which binds specificly to a cell surface molecule. The tagged probe includes a molecular tag that is linked to a first binding compound through a cleavable linkage, and the cleaving probe includes a second binding agent and a cleavage-inducing moiety that can cleave the linkage when within a defined proximity thereto. Binding of the two probes to cell surface molecules that have formed an oligomeric complex results in release of the molecular tag from the binding compound, providing a measure of formation of the complex.

Modified antibodies containing 2 or more H chain V domains and or more L chain V domains of a monoclonal antibody which can transduce a signal into cells by crosslinking a cell surface molecule, thereby serving as an agonist. Because of being usable as agonists for signal transduction, these modified antibodies are useful as, for example, preventives and / or remedies for various diseases such as cancer, inflammation, hormone disorders and blood diseases.

The present invention relates to the field of protein display libraries and library screening. In preferred embodiments, the present invention provides a three component system for display comprising a cell surface molecule, an adapter molecule and a display molecule.

The present invention provides methods for increasing expression of cell surface molecules of CD5+ B cell lymphoma cells by contacting cells with immune response modifiers. The invention also provides methods for the treatment of CD5+ B cell lymphomas, including chronic lymphocytic leukemia and small lymphocytic lymphoma, by administering immune response modifier compounds to a subject in need of such treatment. Suitable immune response modifier compounds include agonists of TLR7 and / or TLR8.

The present invention is directed to the use of agents that induce high levels of cell surface molecules to provide targets for immunotoxins directed against the same cell surface molecules. A specific example is given in which all-trans-retinoic acid (RA) is used to induce high levels of CD38 cell surface antigen expression in several myeloid and lymphoid leukemia cells. CD38 was then used as target for delivering plant toxin (gelonin) to leukemia cells. Treatment of leukemia cells with RA induced high levels of CD38 in those cells that otherwise had low CD38 expression. The RA-induced leukemia cells then became exquisitely sensitive to an immunotoxin constructed from an anti-CD38 monoclonal antibody conjugated to the plant toxin gelonin.

A cell surface molecule that is expressed specifically in thymocytes, lymphocytes activated by ConA-stimulation, and peripheral blood lymphocytes. This molecule is involved in signal transmission of the secondary signal (costimulatory signal) essential for the activation of lymphocytes such as T cells and regulates functions of activated lymphocytes such as activated T cells. Disclosed are a polypeptide of the cell surface molecule; a polypeptide fragment thereof; a fusion polypeptide comprising the fragment; a pharmaceutical composition comprising any one of the above; and methods of using the compositions.

Cells are profiled with respect to their expression of cell surface molecules, and ability to respond to external stimulus in the microenvironment. External stimuli include cell-cell interactions, response to factors, and the like. The cells are arrayed on a planar or three-dimensional substrate through binding to immobilized or partially diffused probes. Probes of interest include specific binding partners for cell surface molecules, signaling cues that act to regulate cell responses, differentiation factors, etc., which may be arrayed as one or a combination of molecules.

Novel cell surface molecules recognized by monoclonal antibodies against a cell surface molecule of lymphocytic cells that play an important role in autoimmune diseases and allergic diseases have been isolated, identified, and analyzed for their functions. The cell surface molecules are expressed specifically in thymocytes, lymphocytes activated by ConA-stimulation, and peripheral blood lymphocytes, and induce cell adhesion. Antibodies against the cell surface molecules significantly ameliorate pathological conditions of autoimmune diseases and allergic diseases.

The present invention relates to a product and process for suppressing an immune response using a T lymphocyte veto molecule capable of blocking cell surface molecules responsible for T cell activation. Disclosed is a CD4 or CD2 molecule, associated with an immunoglobulin molecule capable of binding to a major histocompatibility antigen. Also disclosed is a method to produce a T lymphocyte veto molecule, a therapeutic composition comprising a T lymphocyte veto molecule and methods to use T lymphocyte veto molecules in therapeutic processes requiring suppression of an immune response.

Compounds comprising a diagnostic or therapeutic moiety can be retained inside a cell by conjugating the moiety to at least one PNA that is targeted to the transcripts from a gene of interest. The diagnostic or therapeutic moiety is also conjugated to at least one targeting moiety specific for an extracellular receptor or other cell surface molecule. The targeting moiety binds to the surface of a cell, and the entire compound is then internalized. Once inside the cell, the PNA portion of the diagnostic or therapeutic compound binds to RNA transcripts in a sequence specific manner. Binding of the PNA to its target RNA transcript retains the compound within the cell. The PNA can be designed to bind to a predetermined nucleic acid sequence from an RNA transcript, for example a mutated or overexpressed sequence that is characteristic of a pathological state.

The invention provides methods and kits for detecting and / or measuring receptor homodimers on a cell surface membrane. In one aspect, the methods employ pairs of probes comprising binding compounds and a cleaving probe, such that at least one binding compound binds specifically to the same epitope of a membrane-bound analyte as the cleaving probe. The binding compound includes one or more molecular tags attached through a cleavable linkage, and the cleaving probe includes a cleavage-inducing moiety that can cleave the linkage when within a defined proximity thereto. Binding of the two probes to a homodimer of a cell surface molecules results in release of molecular tags from the binding compounds, providing a measure of formation of the homodimeric complex.

Mutant polypeptides of the present invention contain an Fc region in which a cysteine residue is substituted for the second amino acid from the glycosylation site to the N terminal side in the Fc region. The Fc region is preferably a human IgG Fc region. The mutant polypeptides of the present invention may also contain an N-linked sugar chain at the glycosylation site in Fc region. Furthermore, a polypeptide domain other than the Fc region of the mutant polypeptides of the present invention may be a polypeptide molecule that recognizes a human cell surface molecule.

The susceptibility of human macrophages to human immunodeficiency virus (HIV) infection depends on cell surface expression of the human CD4 molecule and CC cytokine receptor 5. CCR5 is a member of the 7-transmembrane segment superfamily of G-protein-coupled cell surface molecules. CCR5 plays an essential role in the membrane fusion step of infection by some HIV isolates. The establishment of stable, nonhuman cell lines and transgenic mammals having cells that coexpress human CD4 and CCR5 provides valuable tools for the continuing research of HIV infection. In addition, antibodies which bind to CCR5, CCR5 variants, and CCR5-binding agents, capable of blocking membrane fusion between HIV and target cells represent potential anti-HIV therapeutics for macrophage-tropic strains of HIV.

Modified antibodies containing 2 or more H chain V domains and or more L chain V domains of a monoclonal antibody which can transduce a signal into cells by crosslinking a cell surface molecule, thereby serving as an agonist. Because of being usable as agonists for signal transduction, these modified antibodies are useful as, for example, preventives and / or remedies for various diseases such as cancer, inflammation, hormone disorders and blood diseases.

Dysfunctional or exhausted T cells arise in chronic diseases including chronic viral infections and cancer, and express high levels of co-inhibitory receptors. Therapeutic blockade of these receptors has clinical efficacy in the treatment of cancer. While co-inhibitory receptors are co-expressed, the triggers that induce them and the transcriptional regulators that drive their co-expression have not been identified. The immunoregulatory cytokine IL-27 induces a gene module in T cells that includes several known co-inhibitory receptors (Tim-3, Lag-3, and TIGIT). The present invention provides a novel immunoregulatory network as well as novel cell surface molecules that have an inhibitory function in the tumor microenvironment. The present invention further provides the novel discovery that the transcription factors Prdm1 and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the co-expression of co-inhibitory receptors in dysfunctional T cells and identifies novel regulators of T cell dysfunction.

The susceptibility to human immunodeficiency virus (HIV) infection depends on the cell surface expression of the human CD4 molecule and a human fusion accessory factor associated with HIV infection (CXCR4). CXCR4 is a member of the 7-transmembrane segment superfamily of G-protein-coupled cell surface molecules. CXCR4 plays an essential role in the membrane fusion step of HIV infection. The establishment of stable, nonhuman cell lines and transgenic mammals having cells that coexpress human CD4 and CXCR4 provides valuable tools for the continuing research of HIV infection and the development of more effective anti-HIV therapeutics. In addition, antibodies against CXCR4, isolated and purified peptide fragments of CXCR4, and CXCR4-binding biologic agents, capable of blocking membrane fusion between HIV and target cells represent potential anti-HIV therapeutics.

Improved methods, reagents, and kits for quantitation of HLA-DR and / or CD11b expression on peripheral blood cells are presented. Inclusion of a lysosomotropic amine, such as chloroquine, during staining stabilizes HLA-DR and CD11b expression. Use of a novel anti-CD14 conjugate, anti-CD14-PerCP / CY5.5, permits the ready discrimination of monocytes. The improved methods, reagents, and kits may be used to assess immune competence, and to direct and monitor immunostimulatory therapies in septic patients exhibiting monocyte deactivation.

Objects of the present invention are to provide a method for designing an optimum delivery preparation with the use of a convenient experiment and / or assay and to search for the thus produced delivery vehicle. The present invention provides a method for producing a delivery vehicle for achieving the delivery of a desired substance to a desired site, which comprises the steps of:A) measuring in vitro affinity of candidate delivery vehicles for a cell surface molecule such as a lectin associated with the site; andB) selecting a delivery vehicle having in vitro affinity corresponding to delivery to the desired site.

The present invention relates to an engineered immune cell expressing (i) a cell surface molecule that specifically recognizes a ligand, (ii) an exogenous interleukin, and (iii) an exogenous Flt3L, XCL2, and / or XCL1. The invention also provides the use of the engineered immune cell in the treatment of cancer, infection or autoimmune disease. Compared with the traditional engineered immune cell, the engineered immune cell has remarkably improved tumor killing activity.

Disclosed herein are drug delivery molecules that comprise a ligand that targets a cell surface molecule; a membrane penetration domain; and a payload binding domain; and pharmaceutical compositions comprising the same. Also disclosed are methods of treating cancer, inhibiting the progression of cancer, preventing cancer metastasis, and delivering a therapeutic compound to the brain in a subject in need thereof, the methods comprising identifying a subject in need thereof; providing a composition comprising the drug delivery molecule as disclosed herein; and administering an effective amount of the composition to the subject.

Described herein are compositions and methods for treating a disease, particularly a cancer, with primed dendritic cells recognizing a tumor antigen. The methods may comprise storing, shipping and / or culturing dendritic cells, where the dendritic cells are stored on a hard surface. Lysis protocols are described where the lysis does not result in complete lysis of cells in order to provide cell surface molecules maintained in a cell surface-embedded state. Non-lethal Dengue virus strains are also provided for therapeutic purposes.

Disclosed herein are antibody drug conjugates having an antibody or antibody fragment that binds a cell surface molecule on a target cell, wherein the target cell is a lymphocyte and a therapeutic agent that has a therapeutic effect in a subject in need thereof. Further disclosed herein are antibody drug conjugates having an antibody or antibody fragment that binds a cell surface molecule on a target cell; and a therapeutic agent that binds an intracellular moiety of the target cell. These antibody drug conjugates may be used for treating cardiovascular diseases.

The invention provides antibody arrays specific for target antigens. Methods for discovery and compositions comprising native human antibodies, arrays comprising such antibodies, immortalized B cells expressing such antibodies and non-immortalized B cell libraries comprising B cells expressing such antibodies are provided. The invention provides a method for screening monoclonal antibodies for functional effects on cell surface molecules such as receptors using antibody repertoire arrays specific for target cell surface molecules. Functional antibodies directed to a target and therapeutics derived from such antibodies are also provided. High throughput and parallel screening for potentially therapeutic antibodies are provided. Antibodies directed to functional epitope clusters corresponding to a target and vaccines and therapeutics derived from such antibodies are also provided.

Human cell surface molecules CD70 and CD203c are expressed at higher levels in kidney carcinomas, particularly renal cell carcinomas and clear cell renal cell carcinomas, yet are expressed at low levels in normal kidney and other diseased kidney tissue, and at low levels in other tissues. CD70 and CD203c show specificity towards kidney carcinomas, particularly renal cell carcinomas and clear cell renal cell carcinomas and thus can be used as diagnostic markers and therapeutic targets for these diseases. In addition, antibodies or small molecules against these molecules could be used in treatments towards these diseases.

The invention discloses an electrochemiluminescent imaging device which comprises an object lens, a light transmission channel, a single-photon detection electron multiplication CCD (charge coupled device) and an electrochemiluminescent generator, wherein the electrochemiluminescent generator comprises an ITO (indium tin oxide) electrode, a silver electrode and a voltage generator; the object lens, the light transmission channel and the single-photon detection electron multiplication CCD are connected in sequence; the ITO electrode is connected with the positive electrode of the voltage generator; the silver electrode is connected with the negative electrode of the voltage generator. The invention further discloses applications of the electrochemiluminescent imaging device to visual detection on hydrogen peroxide, hydrogen peroxide leaking from the surface of single cells and cell surface molecules. The electrochemiluminescent imaging device is simple in composition, high in detection flux, easy to operate and high in luminous efficiency, and can perform the parallel quick detection.