39 results about "Fc-Gamma Receptor" patented technology

The present invention relates to a non-immunostimulatory antibody which lacks antibody-dependent cell-mediated cytotoxicity, Fc gamma receptor binding and complement-mediated cytotoxicity. In some embodiments, the antibody contains a modified immunoglobulin G2 (IgG2) Fc region with at least one substitution in the B/C loop, FcRn binding domain, and the F/G loop. The antibody of the invention is useful in the preparation of therapeutic antibodies and pharmaceutical compositions and kits containing the same.

Disclosed herein are GNGN and G1/G2 antibodies that recognize and bind various FcRs and C1q. Also disclosed herein are glycan-optiminzed antibodies, predominantly of the GNGN or G1/G2 glycoform, with enhanced Fcγ receptor binding achieved through CHO, Nicotiana benthamiana and yeast manufacturing systems. Nucleic acids encoding these antibodies, as well as expression vectors and host cells including these nucleic acids are also disclosed herein. Methods and pharmaceutical compositions including the monoclonal antibodies are provided herein for the prevention and/or therapeutic treatment of viral infections, cancers and inflammatory diseases.

An objective of the present invention is to provide chimeric receptors containing a mouse Fcγ receptor extracellular domain and a human Fcγ receptor transmembrane domain, or chimeric receptors containing a mouse Fcγ receptor extracellular domain and a human γ chain transmembrane domain. Another objective of the present invention is to provide methods for measuring the ADCC activity of mouse antibodies and methods of screening for mouse antibodies having ADCC activity, using the chimeric receptors.

To accomplish the above-mentioned objectives, the present inventors produced chimeric molecules by fusing the extracellular domain of mouse FcγR3 or mouse FcγR4 with the transmembrane domain/intracellular domain of human γ chain or human FcγR3, and expressed the chimeric molecules in human NK92 cells. It was revealed that the ADCC activity can be induced by the chimeric receptors produced by any combination of the domains, and that the ADCC activity of mouse antibodies can be measured using the chimeric receptors of the present invention.

Methods for the use of Fc gamma receptor (FcγR) polymorphisms as a diagnostic for intervention with interleukin-2 (IL-2) immunotherapy are provided. The methods comprise detecting the allelic pattern of an FcγRIIIA gene or FcγRIIA gene of an individual, and determining whether the allelic pattern is predictive of a positive therapeutic response to IL-2 immunotherapy. The presence of the FcγRIIIA 158F/F homozygous genotype, and/or the presence of one or both copies of the FcγRIIIA 48L allele, and/or the presence of one or both copies of the FcγRIIA 131R allele is predictive of a positive therapeutic response to IL-2 immunotherapy, and therefore indicative of medical intervention with IL-2 immunotherapy for treatment of an immune disorder. The diagnostic method finds use in identifying those individuals whose immune function can be improved by treatment with IL-2 immunotherapy, particularly for individuals with cancer.

The present disclosure relates to a method of treating a solid tumour, wherein said method involves the use of an antibody to CD25. In particular, the antibody to CD25 is optimized for depletion of regulatory T cells (Treg) within tumours. The present invention also provides novel anti-CD25 antibodies and their combination with other anti-cancer drugs, such as immune checkpoint inhibitors, compounds that target cancer antigens or the inhibitory Fc receptor FcyR11b (CD32b).

The present invention relates to binding molecules that specifically bind to the human Fc gamma receptor expressed on the surface of natural killer (NK) cells and macrophages (i.e. Fc Gamma RIIIA), and in particular binding molecules that specifically bind the A form Fc Gamma RIII but do not bind to the B form of Fc Gamma RIII, as well as to the use of such binding molecules in the diagnosis and treatment of disease. The invention further extends to polynucleotides encoding such binding molecules, host cells comprising such polynucleotides and methods of producing binding molecules of the invention using such host cells.

The invention relates to a novel method for the exact determination of the binding of the Fc-part of IgG-antibodies to Fc-gamma receptors, and for the simultaneous examination of the antigen-specificity and the Fc-gamma-receptor activation, as well as specific materials for use in said method. The invention furthermore relates to a method for identifying substances that affect the binding of the Fc-part of IgG-antibodies to Fc-gamma receptors, on the basis of the method for the exact determination of the binding of the Fc-part.

The present disclosure relates to the field of biomedicine, and in particular to a chimeric antigen receptor comprising an Fcgamma receptor I and uses thereof. The chimeric antigen receptor comprisesA) a Fc gamma receptor I extracellular domain, B) a hinge region, C) a transmembrane domain, and D) an intracellular signaling domain. The chimeric antigen receptor can improve the therapeutic effectof antibody drugs through the ADCC effect.

The invention provides antibody heavy chain constant regions with a hinge region modified to reduce binding to Fcγ receptors. The modification occurs within positions 233-236 by replacement of natural residues by glycine(s) and/or deletion(s). Such modifications can reduce binding of an antibody bearing such a constant region to Fcγ receptors to background levels. The constant regions can be incorporated into any format of antibody or Fc fusion protein. Such antibodies or fusion proteins can be used in methods of treatment, particularly those in which the mechanisms of action of the antibody or Fc fusion protein is not primarily or at all dependent on effector functions, as is the case when an antibody inhibits a receptor-ligand interaction or agonizes a receptor.

A method of cell-based therapy for treating an autoimmune disease is disclosed. The method is directed at stimulating leukocytes and/or dendritic cells to interrupt autoimmunity in a host. The method provides a Fcγ receptor-specific complex or a complex which results in the co-crosslinking of Fcγ-chains for treating the leukocytes and/or dendritic cells which are in turn used to elicit an autoimmune interruption response in a subject with an autoimmune disease. The Fcγ receptor-specific complex and/or complex which results in the co-crosslinking of Fcγ-chains is used to treat a biological sample comprising leukocytes and/or dendritic cells from a patient, and upon reintroducing said biological sample to the patient, the pre-treated dendritic cells illicit an autoimmune interruption response in vivo.

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.

An antibody and other Fc-containing molecules with variations in the Fc region with reduced binding to C1q and Fc gamma receptors are provided, which can be used in the treatment of various diseases and disorders.