10 results about "High affinity receptor" patented technology

The application discloses a kind of chimeric proteins, including cytokine and cytokine receptor extracellular domain;Cytokine is embedded in the chimeric region of cytokine receptor extracellular domain, and the chimeric region is located in the flexible connection region of cytokine receptor extracellular domain, or the chimeric region is located in the flexible connection region of the cytokine of cytokine receptor extracellular domain embedded in this cytokine.The application discloses that by selecting suitable chimeric region on CD25 and IL-2 protein, two proteins are divided into different peptide segments, are connected to form a peptide chain, and are expressed to form chimeric protein.It has eliminated or reduced affinity for high-affinity IL-2 receptor (IL-2Rαβγ), and retains / enhances the affinity for medium-affinity IL-2 receptor (IL-2Rβγ).The application also discloses chimeric proteins of IL15RA and IL-15 and chimeric proteins of IL21R and IL21.The application also discloses conjugates, pharmaceutical compositions, nucleic acid molecules, expression vectors, host cells, production methods, kits of the chimeric protein, and uses thereof.

This invention relates to hIL2 orthogonal ligands (“IL2 orthogonal homologs”) that specifically and selectively bind to transmembrane peptides comprising an extracellular domain (ECD) of a modified hCD122 polypeptide. The binding of the hIL2 orthogonal homolog to the modified hCD122 polypeptide participates in intracellular signal transduction pathways, resulting in biological activity associated with the native intracellular signal transduction pattern of hIL2 binding to intermediate- or high-affinity hIL2 receptors, but exhibiting selectivity for engineered hCD122 orthogonal receptors. Compared to its binding to the extracellular domain of wild-type hCD122, the hIL2 orthogonal homologs of this invention exhibit significantly reduced binding, either alone or when hCD122 is present in the form of an endogenous high- or intermediate-affinity hIL2 receptor.

Compositions and methods for treating diseases and conditions mediated by the high affinity IgE receptor (FcεRI) are provided. Also provided are antisense oligomers for modulating splicing of mRNA encoding a MS4A6A protein, optionally in addition to antisense oligomers for modulating splicing of mRNA encoding the FcεRIβ protein, thereby down-regulating cell-surface expression of FcεRI, and uses of the antisense oligomers for inhibiting mast cell degranulation, cytokine release, migration, and proliferation; for inhibiting anaphylaxis reactions in individuals, for treating allergic conditions in individuals, for reducing the incidence of allergic reactions in individuals, for treating individuals at risk of developing anaphylactic reactions, and for treating mast cell-related diseases in individuals.

The invention relates to IL-2 orthologs and methods of use thereof. The present invention relates to an hIL2 orthogonal ligand ("IL2 straight homolog") that specifically and selectively binds to an extracellular domain (ECD) transmembrane polypeptide consisting of a modified hCD122 polypeptide. Binding of a modified hCD122 polypeptide by a straight homolog of hIL2 participates in the transduction pathway of intracellular signaling, resulting in biological activity of the native intracellular signaling pattern associated with binding of hIL2 to a medium or high affinity hIL2 receptor, but exhibiting selectivity for engineered expression of hCD122 orthogonal receptors. The straight homolog of hIL2 of the present invention exhibits significantly reduced binding as compared to its binding to the extracellular domain of wild-type hCD122, either alone, or when hCD122 is present in the form of an endogenous high or medium affinity hIL2 receptor.

The invention relates to a human interleukin-2 (IL-2) variant as well as a derivative and application thereof. The IL-2 variants are obtained by authorized computing software, the affinity to the high affinity receptor IL2R [alpha] [beta] [gamma] being reduced or eliminated while preserving the affinity to the medium affinity receptor IL2R [beta] / [gamma]. The disclosure also relates to human antibody fragment fusion proteins comprising the IL-2 variants, which enhance the activity of the interleukin 2 variants.

Provided in the present invention are an IL-2 mutant protein, a fusion protein or conjugate containing the IL-2 mutant protein, and a pharmaceutical composition containing the IL-2 mutant protein, fusion protein or conjugate. Compared with wild-type IL-2 protein, the IL-2 mutant protein of the present invention eliminates or reduces the affinity for a high-affinity IL-2 receptor and substantially retains the affinity for a medium-affinity IL-2 receptor.

The invention discloses a chimeric protein. The chimeric protein comprises a cell factor and a cell factor receptor extracellular domain, the cytokine is embedded into the chimeric region of the cytokine receptor extracellular domain, and the chimeric region is located in the flexible connection region of the cytokine receptor extracellular domain, or the cytokine receptor extracellular domain is embedded into the chimeric region of the cytokine, and the chimeric region is located in the flexible connection region of the cytokine. Proper chimeric regions are selected on CD25 and IL-2 proteins, the two proteins are divided into different peptide fragments, the peptide fragments are connected to form a peptide chain, and the peptide chain is expressed to form the chimeric protein. The present invention relates to compounds having eliminated or reduced affinity to high affinity IL-2 receptors (IL-2R [alpha] [beta] [gamma]) and retaining / enhancing affinity to medium affinity IL-2 receptors (IL-2R [beta] [gamma]). The invention further discloses a chimeric protein of the IL15RA and the IL-15 and a chimeric protein of the IL21R and the IL21. The invention also discloses a conjugate, a pharmaceutical composition, a nucleic acid molecule, an expression vector, a host cell, a production method, a kit and application of the chimeric protein.

The present invention provides a recombinant multivalent TREM1 agonist, termed Tetra-CNX, designed to engage and activate TREM1 on myeloid cells. The ligand comprises multiple calnexin luminal domains assembled in a multimeric configuration, enabling high-avidity receptor binding and downstream SYK-dependent signaling. Upon activation, Tetra-CNX enhances lysosomal remodeling and promotes efficient antigen uptake, processing, and presentation via MHC class I and II pathways. This invention enables improved priming of CD4+ and CD8+ T cells and facilitates immune activation in contexts requiring enhanced antigen presentation, including but not limited to cancer, infectious diseases, and vaccine responses. Pharmaceutical compositions and methods of use are provided for modulating myeloid cell function and adaptive immunity through TREM1-targeted intervention.

The present application provides a kind of interleukin 2 mutant, fusion protein, antibody or conjugate comprising the mutant and pharmaceutical composition comprising the mutant, fusion protein, antibody or conjugate. Compared with wild type interleukin 2, the mutant eliminates the binding with IL-2R alpha, reduces the binding with IL-2R beta gamma dimer, but maintains the stimulation of tumor immune cells, including but not limited to T cells and NK cells proliferation. The IL-2 mutant of the present application eliminates the affinity for high affinity IL-2 receptor, while reducing the affinity for medium affinity IL-2 receptor. The interleukin 2 mutant of the present application is more suitable for fusion protein, antibody conjugate. The mutation site of the interleukin 2 mutant of the present application is very few relative to wild type interleukin 2, so the potential immunogenicity is very low. At the same time, there is no various side effects produced by immunotherapy with natural IL-2.

This invention relates to hIL2 orthogonal ligands (“IL2 orthogonal homologs”) that specifically and selectively bind to transmembrane peptides comprising an extracellular domain (ECD) of a modified hCD122 polypeptide. The binding of the hIL2 orthogonal homolog to the modified hCD122 polypeptide participates in intracellular signal transduction pathways, resulting in biological activity associated with the native intracellular signal transduction pattern of hIL2 binding to intermediate- or high-affinity hIL2 receptors, but exhibiting selectivity for engineered hCD122 orthogonal receptors. Compared to its binding to the extracellular domain of wild-type hCD122, the hIL2 orthogonal homologs of this invention exhibit significantly reduced binding, either alone or when hCD122 is present in the form of an endogenous high- or intermediate-affinity hIL2 receptor.