47 results about "Interleukin II" patented technology

The invention relates to development and application of a novel interleukin 2 (IL-2) mutant and an anti-PD-1 / anti-VEGF fusion protein of the IL-2 mutant, compared with wild type IL-2, the IL-2 mutant has optimized IL-2 receptor binding capacity, the invention further provides the fusion protein containing the IL-2 mutant, and the fusion protein containing the IL-2 mutant can be used for preparing the anti-PD-1 / anti-VEGF fusion protein. Polynucleotides encoding the fusion proteins, nucleic acid constructs, host cells and pharmaceutical compositions and therapeutic uses thereof.

The invention provides a human interleukin 2-polyethylene glycol conjugate and use thereof. The human interleukin 2-polyethylene glycol conjugate provided by the invention comprises a recombinant human interleukin 2 containing at least one unnatural amino acid and PEG coupled to the at least one unnatural amino acid. The unnatural amino acid is a compound containing a carbonyl terminal group and having a structure as shown in formula (I) or an enantiomer thereof, and the PEG is coupled to the at least one unnatural amino acid by forming an oxime bond between the carbonyl terminal group and the PEG containing a hydroxylamine terminal group. The human interleukin 2-polyethylene glycol conjugate provided by the invention can be used individually or in combination with other anti-tumor drugs for the treatment of diseases such as solid tumors and hematologic tumors.

The present invention relates to a bifunctional molecule formed by fusion of a PD1 antibody and interleukin 2, comprising: a heterodimer composed of a first monomer and a second monomer as follows: (1) a first monomer, formed by linking interleukin 2 (IL2) to an immunoglobulin Fc single chain; and (2) a second monomer, formed by linking an Fab / ScFv of an anti-T cell surface molecule antibody to an Fc single chain. The bifunctional molecule may also be a homodimer comprising a monomer comprising: (1) an interleukin 2 functional block; and (2) a monomer of an antibody or a monomer formed by linking an Fab / ScFv of an antibody to an Fc single chain, the antibody being an anti-T cell surface molecule antibody. The present invention further relates to use of the bifunctional molecule in the manufacture of anti-tumor medicament.

The present invention relates to a bifunctional molecule formed by fusion of a PD1 antibody and interleukin 2, comprising: a heterodimer composed of a first monomer and a second monomer as follows: (1) a first monomer, formed by linking interleukin 2 (IL2) to an immunoglobulin Fc single chain; and (2) a second monomer, formed by linking an Fab / ScFv of an anti-T cell surface molecule antibody to an Fc single chain. The bifunctional molecule may also be a homodimer comprising a monomer comprising: (1) an interleukin 2 functional block; and (2) a monomer of an antibody or a monomer formed by linking an Fab / ScFv of an antibody to an Fc single chain, the antibody being an anti-T cell surface molecule antibody. The present invention further relates to use of the bifunctional molecule in the manufacture of anti-tumor medicament.

The application provides an anti-human interleukin 2 monoclonal antibody, a CBA kit comprising the antibody and a detection method thereof. Specifically, the application provides an antibody against human interleukin 2 and a CBA kit comprising the antibody. The kit provided by the application can complete quantitative detection of human interleukin 2, has high specificity and detection sensitivity, and has a good development and application prospect.

The present invention provides, among other things, a masked cytokine comprising an interleukin 2 (IL-2) polypeptide, a VHH masking moiety, an anti-PD1 targeting moiety, and an engineered Fc domain comprising a tumor-associated protease cleavage site. In such masked cytokine, the IL-2 polypeptide is engineered to be activatable by a protease at a target site, such as in a tumor microenvironment. The VHH masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavage site in the Fc domain, the IL-2 polypeptide becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

The present invention relates to a method for amplifying an invariant natural killer T (iNKT) population and an application thereof, the method comprising: providing a peripheral blood stem cell sample; culturing the peripheral blood stem cell sample in an amplification culture medium, wherein the amplification culture medium comprises interleukin 2, interleukin 15 and alpha-galactosylceramide; and adjusting the number of the cultured cells, and co-culturing the cultured cells and feeder cells in the amplification medium, the feeder cells being a dendritic cell and a peripheral blood mononuclear cell.

The present invention relates to the field of Biotechnology, particularly to a method based on the introduction of a single mutation in the genes encoding the human IL-2 and the muteins derived thereof that results in increased secretion levels in different hosts without affecting their biological functions. In particular, these mutations are based on a non-conservative change in the amino acid located in position 35 in the primary sequence of human IL-2, preferably the substitutions are K35E, K35D and K35Q. Another object of the present invention are the expression systems used to obtain both the recombinant human IL-2 and the muteins derived thereof using the method described in this invention. The above-mentioned method is useful to improve the production efficiency of the recombinant human IL-2 and the muteins derived thereof both at laboratory and industrial scales. The proteins obtained using this method can be used for therapeutic purposes as well as in the in vitro expansion of T cells for adoptive transfer therapies.

The present invention discloses a preparation method and application of transplanted tumor tissues, belonging to the field of biotechnology. Also disclosed is a reagent combination for preparing transplanted tumor tissues, including PMA and interleukins, wherein the interleukins include interleukin 2, interleukin 10 and interleukin 12. By using the reagent combination, kit and method of the present invention to prepare transplanted tumor tissues and further prepare quality control products, complex operations are not required, nor are a large number of consumables, culture equipment and culture space needed, which is very convenient for large-scale production; the transplanted tumor tissues of the present invention not only have stable sources and properties, but also the transplanted tumors have tissue-like morphology. When prepared into quality control products, they can provide more information in pathological interpretation. They can not only be used to monitor the process of immunohistochemistry experiments, but also assist in interpreting pathological results, and have very important clinical application value.

The present invention provides, among other things, a masked cytokine comprising an interleukin 2 (IL-2) polypeptide, a VHH masking moiety, an anti-PD1 targeting moiety, and an engineered Fc domain comprising a tumor-associated protease cleavage site. In such masked cytokine, the IL-2 polypeptide is engineered to be activatable by a protease at a target site, such as in a tumor microenvironment. The VHH masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavage site in the Fc domain, the IL-2 polypeptide becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

The present disclosure relates, inter alia, to polynucleotides encoding modified interleukin 2 (IL-2) polypeptides and fusion proteins comprising such modified IL-2 polypeptides, vectors comprising such polynucleotides, pharmaceutical compositions comprising such polynucleotides and vectors, pharmaceutical compositions comprising such polynucleotides, and pharmaceutical compositions comprising such polynucleotides. And methods of treating diseases and conditions by administering such polynucleotides, vectors, and / or pharmaceutical compositions.

The application discloses a chicken interleukin 2 antibody and application thereof, the antibody comprises a light chain and a heavy chain variable region, the amino acid sequences of three complementarity determining regions in the light chain variable region are respectively shown as SEQ ID NO. 1-3, the amino acid sequences of three complementarity determining regions in the heavy chain variable region are respectively shown as SEQ ID NO. 5-7, or the amino acid sequences of three complementarity determining regions in the light chain variable region are respectively shown as SEQ ID NO. 17-19, and the amino acid sequences of three complementarity determining regions in the heavy chain variable region are respectively shown as SEQ ID NO. 21-23. The antibody provided by the application has the advantages of high effective value, good specificity, high affinity and reaction with natural ChIL-2 antigen. The ChIL-2 double antibody sandwich enzyme-linked immunosorbent assay (ELISA) established based on the two antibodies has the advantages of high specificity, high sensitivity, simple operation and good repeatability, and can be used for determination of the ChIL-2 content in cell culture supernatant, chicken serum and other samples.

The present invention provides, among other things, a masked cytokine comprising an interleukin 2 (IL-2) polypeptide, a VHH masking moiety, an anti-PD1 targeting moiety, and an engineered Fc domain comprising a tumor-associated protease cleavage site. In such masked cytokine, the IL-2 polypeptide is engineered to be activatable by a protease at a target site, such as in a tumor microenvironment. The VHH masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavage site in the Fc domain, the IL-2 polypeptide becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

Provided is a cytokine combination useful for treating a tumor and / or preventing recurrence or metastasis of the tumor. The cytokine combination with at least three cytokines selected from the following groups: interleukin 12 (IL12) or a functional variant thereof, granulocyte-macrophage colony-stimulating factor (GMCSF) or a functional variant thereof, FMS-like tyrosine kinase 3 ligand (FLT3L) or a functional variant thereof, interleukin 2 (IL2) or a functional variant thereof, interleukin 15 (IL15) or a functional variant thereof, interleukin 21 (IL21) or a functional variant thereof, and interleukin 7 (IL7) or a functional variant thereof. Also provided is a nucleic acid molecule encoding the cytokine combination and a vector thereof, a cell, a pharmaceutical composition, and a application thereof for the manufacture of a drug for treating the tumor and / or preventing recurrence or metastasis of the tumor.

In the research, modified silk fibroin (SF-TK), methacrylamide gelatin (GelMA) and quaternary ammonium salt chitosan (QCS) are taken as matrix hydrogel (GCS), metformin (Met) and IL2-loaded PLGA particles (IL2-coated PLGA) are loaded, Met can promote polarization of macrophages from M1 to M2, interleukin 2 with a specific concentration can specifically promote proliferation of Regulatory T cells (Tregs for short), and the Met and IL2-loaded PLGA particles (IL2-coated PLGA) can be used for preparing an anti-inflammatory drug for treating the macrophages. Due to different loading modes of the metformin and the interleukin, the highest peak values accumulated by concentration of the metformin and the interleukin appear in a staggered manner, so that the effect that macrophages are polarized firstly and then Tregs are proliferated is achieved, and different immune cells can be adjusted in a time sequence manner, so that wound healing is promoted. The research starts from two immune cells in a wound microenvironment, macrophage polarization and Tregs proliferation are sequentially induced, angiogenesis is promoted through paracrine action of the immune cells, and diabetic chronic wound repair is sequentially promoted.

The application relates to the treatment of cancer, including non-melanoma skin cancer. The invention involves the use of a tumor necrosis factor alpha (TNFα) immunoconjugate and an interleukin 2 (IL2) immunoconjugate in a combination therapy for the treatment of non-melanoma skin cancer.

The invention belongs to the field of biotechnology and veterinary immune preparations, and relates to a porcine IL-2-IFN-alpha-T alpha 1 interferon fusion protein and a preparation method and application thereof.The amino acid sequence of the interferon fusion protein is shown as SEQ ID NO.1, and the interferon fusion protein is composed of recombinant porcine interleukin 2, flexible connecting peptide, recombinant porcine alpha interferon, flexible connecting peptide and thymosin; the amino acid sequence of the recombinant porcine interleukin 2 is as shown in SEQ ID NO. 2; the amino acid sequence of the recombinant porcine alpha interferon is as shown in SEQ ID NO.3; the amino acid sequence of the thymosin is as shown in SEQ ID NO. 4; the amino acid sequence of the flexible connecting peptide is as shown in SEQ ID NO.5. The porcine IL-2-IFN-alpha-T alpha 1 interferon fusion protein provided by the invention has good biological activity and no cytotoxicity, has high antiviral property and immune regulation function, and can effectively improve the antiviral ability of pigs.

The application discloses interleukin 2 mutants and application thereof, and the application introduces at least one amino acid mutation to change the binding of IL-2 to different receptors by structural analysis of IL-2 and its three receptors, computer-aided design technology, modeling and molecular docking. In the construction of the designed different IL-2 mutants, expression, purification and function analysis are carried out to confirm that the mutants do not bind to IL-2R alpha receptor, but basically do not affect the binding to IL-2R beta / gamma receptor complex. The mutants provided by the application can better activate Teff cells and NK cells, instead of preferentially activating Treg cells with inhibitory function like wild-type IL-2, and the mutants of IL-2 can better play an anti-tumor role in vivo.

This disclosure relates to, inter alia, polynucleotides encoding modified interleukin 2 (IL-2) polypeptides and fusion proteins comprising such modified IL-2 polypeptides, vectors comprising such polynucleotides, pharmaceutical compositions comprising such polynucleotides and vectors, and methods of treating diseases and disorders by administering such polynucleotides, vectors, and / or pharmaceutical compositions.

The present invention relates to a long-acting conjugate of an interleukin-2 analog with altered binding affinity for interleukin-2 receptors.

The present disclosure relates to methods of treating cancer with the combination of a binding protein comprising a first and a second antigen binding domain (ABD), wherein the first ABD binds specifically to human CD123 and the second ABD binds specifically to human NKp46, and an interleukin 2 (IL-2) polypeptide.

The present invention relates to a cell line wherein the endogenous class I and / or class II HLA alleles are inactivated, the cell line further comprising (a) a polynucleotide encoding a first fluorescent marker under control of at least one STAT response element, and (b) an interleukin 2 (IL-2) receptor. The invention further relates to the use of said cell line for the identification of antigenic peptide and / or the identification of alloreactive T cell receptors.

The present invention provides, among other things, a masked cytokine comprising an attenuated interleukin 2 (IL-2) polypeptide, a VHH masking moiety, a carrier moiety, and an anti-PD1 targeting moiety. In some embodiments, the IL-2 polypeptide is engineered with a proteolytically cleavable linker comprising to be activated at a target site, such as in a tumor microenvironment, by protease activity. The VHH masking moiety blocks, occludes, inhibits (e.g., reduces), or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. When the cleavable linker is proteolytically cleaved at the target site, the IL-2 polypeptide is activated, which enables it to bind to its cognate receptor or protein with increased affinity.

A human interleukin 2-polyethylene glycol conjugate and use thereof. The human interleukin 2-polyethylene glycol conjugate comprises a recombinant human interleukin 2 containing at least one unnatural amino acid and PEG coupled to the at least one unnatural amino acid. The unnatural amino acid is a compound containing a carbonyl terminal group and having a structure as shown in formula (I) or an enantiomer thereof, and the PEG is coupled to the at least one unnatural amino acid by forming an oxime bond between the carbonyl terminal group and the PEG containing a hydroxylamine terminal group. The human interleukin 2-polyethylene glycol conjugate can be used individually or in combination with other anti-tumor drugs for the treatment of diseases such as solid tumors and hematologic tumors.

The present invention provides, among other things, a masked cytokine comprising an interleukin 2 (IL-2) polypeptide, a VHH masking moiety, an anti-PD1 targeting moiety, and an engineered Fc domain comprising a tumor-associated protease cleavage site. In such masked cytokine, the IL-2 polypeptide is engineered to be activatable by a protease at a target site, such as in a tumor microenvironment. The VHH masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavage site in the Fc domain, the IL-2 polypeptide becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

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.

The present invention provides, among other things, a masked cytokine comprising an interleukin 2 (IL-2) polypeptide, a VHH masking moiety, an anti-PD1 targeting moiety, and an engineered Fc domain comprising a tumor-associated protease cleavage site. In such masked cytokine, the IL-2 polypeptide is engineered to be activatable by a protease at a target site, such as in a tumor microenvironment. The VHH masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavage site in the Fc domain, the IL-2 polypeptide becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

The invention belongs to the field of genetic engineering and immunology, and particularly relates to a glucagon-like peptide-1-human interleukin 2 fusion protein as well as a preparation method, a product and application of the glucagon-like peptide-1-human interleukin 2 fusion protein. Specifically, a gene molecule cloning technology is utilized, a gene sequence of a fusion protein molecule of GLP-1-IL2-Fc and GLP-1-IL2 (glucagon-like peptide-1-human interleukin 2) introduced into an HEK293F cell is optimized, and two fusion proteins of GLP-1-IL2 and GLP-1-IL2 are successfully constructed and expressed. The GLP-1-IL2-Fc and GLP-1-IL2 bifunctional fusion protein prepared by the invention can bias stimulate the retention and proliferation of Foxp3 + T cells in pancreas and reduce the infiltration of CD8 + T cells, and meanwhile, the GLP-1 can also promote the proliferation of pancreatic beta cells and increase the quality of the pancreatic beta cells, and can be used for preventing the development of type 1 diabetes mellitus.

Provided is a site-specific PEG-modified interleukin 2 (IL-2) mutant. Compared with a parent IL-2, the mutant has an improved preference for a Treg cell and a prolonged half-life period. Also provided are a composition comprising the IL-2 mutant, a nucleic acid encoding the IL-2 mutant, a vector comprising the nucleic acid, and a host cell. Further provided are the IL-2 mutant and therapeutic use of a pharmaceutical composition comprising same.

The present disclosure provides novel interleukin 2 (IL-2) muteins. Also provided are fusion proteins, immunoconjugates comprising the IL-2 muteins, as well as nucleic acids encoding the IL-2 muteins, vectors and host cells comprising the nucleic acids. Further provided are methods of making the IL-2 muteins, pharmaceutical compositions comprising the IL-2 muteins and therapeutic uses of the muteins.