72 results about "Fc receptor" patented technology

This invention is directed to treatment of a subject having or suspected of having a cancer comprising administering to the subject a monoclonal antibody and NK-92 expressing Fc receptor.

Antibodies, antigen-binding proteins and Fc-fusion proteins that comprise recombinant polypeptides containing a chimeric heavy chain constant region sequence are provided that bind to certain Fc receptors however have reduced effector functions. Methods of making constructs for expression of such chimeric Fc-containing antibodies, antigen-binding proteins and Fc-fusion proteins in cell systems, and methods of producing and isolating the chimeric Fc-containing proteins are provided.

The present disclosure provides a method for enhancing the anti-tumor efficacy of an Fc fusion protein which binds specifically to a target, e.g., a co-inhibitory or co-stimulatory receptor of ligand, on a T cell in a subject afflicted with a cancer or a disease caused by an infectious agent and alters the activity of the immunomodulatory target, thereby potentiating an endogenous immune response against cells of the cancer or the infectious agent, wherein the method comprises selecting, designing or modifying the Fc region of the Fc fusion protein so as to enhance the binding of said Fc region to an activating Fc receptor (FcR). The disclosure also provides an Fc fusion protein produced by said method and its use in treating a subject afflicted with a cancer or a disease caused by an infectious agent.

This invention is directed to treatment of a subject having or suspected of having a cancer comprising administering to the subject a monoclonal antibody and NK-92 expressing Fc receptor.

The disclosure provides Fc polypeptides wherein the Fc domain comprises at least one amino acid substitution that reduces binding affinity to an Fc receptor and / or effector function comprising one or more, two or more, three or more, four or more, or all five amino acid substitutions selected from L234A, L235A, G237A, K322A, and P329G, wherein the residues are numbered according to the EU index, preferably wherein the Fc polypeptide is an antibody. In some embodiments, the antibody is an anti-GIP antibody. In some embodiments, the antibody further comprises the three M252Y, S254T and T256E substitutions or the two M428L and N434S substitutions, which extend the half-life of the antibody.

To provide an effective cancer therapy that targets both the tumor cells and the cells in the tumor microenvironment.SOLUTION: A recombinant NK-92 cell comprises a recombinant nucleic acid encoding a recombinant chimeric antigen receptor (CAR) that binds to PD-L1, an Fc receptor, and a suicide gene, wherein the recombinant NK-92 cell expresses the CAR and the Fc receptor on its surface.SELECTED DRAWING: Figure 2

Fully human monoclonal Abs includes (i) an antigen-binding variable region that exhibits very high binding affinity for IL-1α and (ii) a constant region that is effective at both activating the complement system though C1q binding and binding to several different Fc receptors.

Disclosed is a polypeptide dimeric protein containing two monomers, each of which contains an extracellular domain (FcεRIa-ECD) of an alpha subunit of an IgE Fc receptor. The dimeric protein has advantages that an excellent binding ability to IgE is exhibited as compared with a conventional therapeutic agent containing an anti-IgE antibody, and less other side effects are exhibited due to lack of ADCC and CDC functions. Thus, the dimeric protein can be applied to a medical product for treating or preventing an IgE-mediated allergic disease.

The present invention relates to antibodies that bind to IgE and their use in the treatment of autoimmune diseases, particularly Bullous Pemphigoid (BP) and Chronic Spontaneous Urticaria (CSU). The anti-IgE antibodies comprise a variant Fc domain that binds to the Fc receptor FcRn with increased affinity relative to a wild-type Fc domain. The anti-IgE antibodies may comprise a variant Fc domain comprising the amino acids Y, T, E, K, F and Y at EU positions 252, 254, 256, 433, 434 and 436, respectively, wherein the variant Fc domain binds to human FcRn with increased affinity relative to a wild-type human IgG Fc domain.

The present invention relates to antibodies that bind to IgE and their use in the treatment of autoimmune diseases, particularly Bullous Pemphigoid (BP) and Chronic Spontaneous Urticaria (CSU). The anti-IgE antibodies comprise a variant Fc domain that binds to the Fc receptor FcRn with increased affinity relative to a wild-type Fc domain. The anti-IgE antibodies may comprise a variant Fc domain comprising the amino acids Y, T, E, K, F and Y at EU positions 252, 254, 256, 433, 434 and 436, respectively, wherein the variant Fc domain binds to human FcRn with increased affinity relative to a wild-type human IgG Fc domain.

Antibodies that target VZV glycoprotein E (gE) bind to recombinant gE with high affinity, bind to gE on the surface of VZV infected cells, interact with immune system effectors (e.g., Fc receptors), mediate antibody-dependent cellular cytotoxicity (ADCC) as well as Antibody Dependent Cellular Phagocytosis (ADCP), and prevent VZV infection of cells.

The presently disclosed subject matter provides fully human antibodies or antigen-binding fragments thereof that bind to FcRL5 and methods of using the same.

The present invention relates to bispecific binding agents comprising an F-actin binding moiety and an Fc domain for use in medicine, which allows for simultaneous binding of an Fc receptor and F-actin. This allows necrotic cell antigens to be presented to the immune system. The invention also provides bispecific binding agents and methods of using the agent to identify a tumour antigen.

The present application relates to the technical field of biological medicine, and more particularly to a multifunctional antibody K1932 binding human CD19, CD3 and Fc gamma R, wherein the multifunctional antibody is composed of a bivalent Fab fragment specifically recognizing CD19 on the surface of B lymphocyte, a bivalent single-chain antibody recognizing CD3 molecule on the surface of T lymphocyte, and a human immunoglobulin Fc domain binding with Fc receptor, wherein the single-chain antibody recognizing CD3 molecule is connected with the C-terminal of Fab light chain through a connecting peptide Linker1, and the heavy chain and the light chain of the CD3 single-chain antibody are connected by a flexible Linker2; the biological macromolecule with the three functional domains is a highly directional immunotherapy drug, which is suitable for injection administration, can guide T cells to attack CD19-positive B lymphocytes, and the Fc domain is combined with Fc gamma R, so that the in-vivo half-life of the biological macromolecule is adjusted and the unnecessary influence on normal cells is reduced.

The present invention provides a polypeptide dimeric protein containing two monomers, each of which contains an extracellular domain (FcεRIa-ECD) of an alpha subunit of an IgE Fc receptor. The dimeric protein according to the present invention has advantages that an excellent binding ability to IgE is exhibited as compared with a conventional therapeutic agent containing an anti-IgE antibody, and less other side effects are exhibited due to lack of ADCC and CDC functions. Thus, the dimeric protein can be applied to a medical product for treating or preventing an IgE-mediated allergic disease.

Fully human monoclonal Abs includes (i) an antigen-binding variable region that exhibits very high binding affinity for IL-1α and (ii) a constant region that is effective at both activating the complement system though C1q binding and binding to several different Fc receptors.

Antibodies targeting VZV glycoprotein E (gE) bind to recombinant gE with high affinity, bind to gE on the surface of VZV infected cells, interact with immune system effectors (e.g., Fc receptors), mediate antibody dependent cytotoxicity (ADCC) and antibody dependent cytophagy (ADCP), and prevent VZV infection of cells.

Fully human monoclonal Abs includes (i) an antigen-binding variable region that exhibits very high binding affinity for IL-1α and (ii) a constant region that is effective at both activating the complement system though C1q binding and binding to several different Fc receptors.

A recombinant natural killer (NK)-92 cell transfected with a nucleic acid and gamma (γ) irradiated, wherein the nucleic acid encodes: a homing receptor and / or cytokine; an antigen binding protein or c

A T cell expressing an FC gamma receptor is provided. Accordingly there is provided a T cell genetically engineered to express a first polypeptide comprising an amino acid sequence of an Fc receptor common γ chain (FcRγ), said amino acid sequence is capable of transmitting an activating signal; and a second polypeptide comprising an extracellular ligand-binding domain of an Fcγ receptor capable of binding an Fc ligand and an amino acid sequence capable of recruiting said first polypeptide such that upon binding of said Fc ligand to said extracellular ligand-binding domain of said Fcγ receptor said activating signal is transmitted.

Provided herein are methods and compositions related to in vivo testing of therapeutic agents comprising a human Fc in genetically modified rodents (e.g., testing the pharmacokinetic and / or pharmacodynamic properties of such therapeutic agents in genetically modified rodents). In some embodiments, the genetically modified rodents express antibodies comprising a human Fc (e.g., human IgG1 Fc, human IgG4 Fc). In some embodiments, the rodents express fully human antibodies (i.e., antibodies having human heavy chains and human light (γ or κ) chains). In certain embodiments, the genetically modified rodent comprises one or more Fc receptors with human extracellular domains (e.g., neonatal Fc receptor (FcRn), β-2-microglobulin polypeptide (β2M), Fcε receptor 1α (FcεR1α), Fcγ receptor 1α (FcγR1a), Fcγ receptor 2a (FcγR2a), Fcγ receptor 2b (FcγR2b), Fcγ receptor 3a (FcγR3a), Fcγ receptor 3b (FcγR3b), Fcγ receptor 2c (FcγR2c)). The transmembrane and cytoplasmic domains of the receptor can be human or non-human (e.g., rodent).

A method for enhancing the immunogenicity of a protein / peptide antigen is provided, wherein the protein / peptide antigen forms a fusion protein with an Fc fragment, preferably with receptor-binding / complement-binding enhanced Fc fragment, and further forms a fusion protein glycoconjugate with a glycosyl group. In the preferred embodiment, the Fc fragment, due to alterations in its amino acid sequence and / or glycosylation, has an enhanced binding capacity to Fc receptors and / or complement protein C1q compared to its native form. Such vaccines can maintain long-term humoral and cellular immune responses, exhibiting higher cellular immune responses and producing higher titers of neutralizing antibodies in immunized animals. Using the SARS-CoV-2 RBD region as the antigen in an immunizing composition, it is formed into a fusion protein with an Fc region that has undergone amino acid sequence and fucose alteration, and further forms a fusion protein glycoconjugate with pneumococcal polysaccharide, for the prevention of SARS-CoV-2 infection-related diseases.

The disclosure relates to a method of detecting the presence of tumor infiltrating Fc receptor-expressing immune cells in a mammalian subject afflicted with a cancer or detecting the presence of one or more site(s) of inflammation characterized by Fc receptor-expressing immune cells in a mammalian subject afflicted with an inflammatory disease or disorder, the method comprising administering a non-specific imaging probe comprising one or more Fc domain(s) labeled with a detectable moiety to the subject; subjecting the subject to imaging; and identifying one or more tumor(s) or sites of inflammation comprising infiltrating Fc receptor-expressing immune cells.

Disclosed herein are compositions comprising a population of silk fibroin nanoparticles having a polydispersity index (PDI) of 0.5 or less, including but not limited to, a PDI of 0.450 or less, 0.40 or less, 0.35 or less, 0.325 or less, 0.30 or less, 0.275 or less, 0.250 or less, 0.225 or less, or 0.200 or less, wherein a glucagon-like peptide-1 (GLP-1) compound or other protein drug or peptide drug including but not limited to insulin, monoclonal antibodies, and related structures is embedded within the population of silk fibroin nanoparticles, wherein the population of silk fibroin nanoparticles is optionally surface treated with at least one of polyethylene glycol, human transferrin protein, the Fc receptor of IgG, or other novel surface modifiers including but not limited to peptides, proteins, or nanobodies. Methods of making and administering the compositions are described herein.

The present invention relates to an extracorporeal method for removing tumor cells from intraoperatively collected blood, wherein trifunctional antibodies are used to bind leukocytes, tumor cells and Fc receptor positive cells. The invention also relates to the use of the above-mentioned extracorporeal method for removing tumor cells from intraoperatively collected blood, followed by reintroducing the purified blood or the red blood cell concentrate purified by this method into the patient from which the intraoperatively collected blood was obtained.

The ICAM-1 / CD54 protein has been found to be a suppressor of antibody-mediated humoral immunity facilitated through its direct binding to the CH3 domain within IgG1 heavy chains. Its binding suppresses antibody immune-effector activity by reducing IgG1 engagement with Fc receptors on effector cells and C1q complement initiating protein. In addition, its binding has the potential to reduce antibody drug conjugate activity by slowing target cell internalization. Engineered antibodies with CH3 region modifications can be generated that reduce or eliminate ICAM-1 / CD54 binding leading to antibodies with improved immune-effector activity and antibody drug conjugate killing in the presence ICAM-1 / CD54. These antibodies can be useful to treat patients with cancer and inflammatory and infectious diseases exhibiting elevated ICAM-1 / CD54 levels.

A recombinant immune cell expresses a heterologous IgG Fc receptor. In some embodiments, the heterologous IgG Fc receptor can be a chimeric IgG Fc receptor. Generally, the chimeric IgG Fc receptor includes an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain generally includes a sufficient portion of CD64 to bind to an IgG Fc region. The intracellular domain of the chimeric IgG Fc receptor includes a sufficient portion of an Fc receptor allowing immunoreceptor tyrosine-based activation motif (ITAM) to initiate cell signaling when an IgG Fc region binds to the extracellular domain.

Multivalent anti-platelet glycoprotein I(b)alpha antibodies can cause severe side effects. The present disclosure provides humanized antibodies specifically recognizing glycoprotein I(b)alpha and lacking a Fc portion, therefore Bleeding Time do not interact with Fc receptor. The humanized antibodies are capable of preventing platelet activation and aggregation, and reducing thrombus size / growth and prevent vessel occlusion. They can be also very useful to decrease platelet-tumor cell interaction and decrease tumor metastasis. At therapeutic doses, the humanized antibodies lack the ability to induce platelet activation, induce thrombocytopenia; and / or prolong bleeding time.

The present disclosure relates to a polypeptide containing an Fc domain in which a part of an amino acid sequence of a human antibody Fc domain is substituted with another amino acid sequence, or an aglycosylated antibody containing the same. The Fc domain of the present disclosure is optimized by substituting a part of an amino acid sequence of a wild-type Fc domain with another amino acid sequence. Therefore, it is useful in treatment of cancer due to superior selective binding ability to FcγRIIIa among Fc receptors, and can be prepared as a homogeneous aglycosylated antibody through bacterial culture.

Fully human monoclonal Abs includes (i) an antigen-binding variable region that exhibits very high binding affinity for IL-1α and (ii) a constant region that is effective at both activating the complement system though C1q binding and binding to several different Fc receptors.