24 results about "Interleukin II" patented technology

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 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 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 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.

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 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.

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 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.

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.

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 application provides a method, composition, kit and use for detecting interleukin 2 positive type 1 helper T cells (IL-2 + Th1 cells) and / or CD4 + CD25 hi CD127 low regulatory T cells (CD4 + Treg cells). The proportion of IL-2 + Th1 cells is increased and the proportion of CD4 + Treg cells is decreased, which has potential value for independently diagnosing early optic nerve compressive lesions, and the diagnostic efficiency of combined detection of the two kinds of cells is much higher than single detection.

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.

A virus vector comprises a constitutive promoter, a nucleic acid sequence encoding a chimeric antigen receptor (CAR), an inducible promoter comprising N nuclear factor of activated T-cells (NFAT) binding motifs followed by the minimal human interleukin 2 (IL-2) promoter, and a nucleic acid sequence encoding a Helicobacter pylori neutrophil activating protein (HP-NAP) and / or an immunological equivalent fragment thereof. The virus vector may be provided in a T-cell useful in T-cell immunotherapy. The T-cells have improved effects in immunotherapy including treating, reducing and / or preventing cancer in a patient.

The present disclosure relates to modified interleukin 2 (IL-2) polypeptides, polynucleotides, e.g., DNA, RNA, or viral vectors, encoding and configured to express the modified IL-2 polypeptides in vitro and / or in vivo, conjugates comprising the modified IL-2 polypeptides, and uses thereof.

The invention discloses an adeno-associated virus AAV vector. The adeno-associated virus AAV vector comprises a cytokine gene, the cell factor is selected from any one or more than two of the following components: human interleukin 2 (IL2), human interleukin 3 (IL3), human interleukin 6 (IL6), human interleukin 15 (IL15), human thrombopoietin (THPO), human stem cell factor (SCF) and human granulocyte-macrophage colony stimulating factor (GM-CSF). The invention also discloses an AAV vector combination comprising any two or more than three AAV vectors mentioned above. The invention also discloses an application of the AAV vector and a combination of the AAV vector in construction of immune system humanized non-human animals. The invention further discloses a method for constructing the immune system humanized non-human animal.

To provide modified IL2 polypeptides and fusion proteins thereof. Methods of modulating immune responses by administering modified IL2 polypeptides or fusion proteins thereof are also provided.SOLUTION: Disclosed is a modified interleukin 2 (IL2) polypeptide comprising a modified IL2R receptor beta (IL2 beta) binding region 2 comprising X1 - X2 - X3 - D - X4 - X5 - X6 - X7 - X8 - X9 - X10 - X11 - X12 - X13 (SEQ ID NO: 1). Wherein X1, X3, X6, X8, X12, and X13 each comprise any residues; X2, X4, and X10 are uncharged residues; X5, X7, X9, and X11 each comprise uncharged apolar residues. Modified IL2 polypeptides and fusion proteins thereof exhibit increased binding to IL2R β, decreased binding to IL2R α, or both.SELECTED DRAWING: Figure 1A

The present invention relates to a formulation of an immune complex ("αPD-1 / IL2m") comprising a recombinant anti-programmed cell death receptor 1 (PD-1) antibody and mutant interleukin 2 (IL2), particularly a stable liquid formulation, a method for preparing the formulation, and the use of the formulation in the treatment and / or prevention of disease.

The present invention relates to a human interleukin 2 (hIL-2) mutein, wherein the hIL-2 mutein is a partial agonist of hIL-2 and has an amino acid sequence identical to SEQ ID NO: 1, except for: (i) the L18R and Q22E substitutions; (ii) an amino acid substitution at position Q126 selected from the group consisting of Q126H and Q126K; and (iii) an N-terminated deletion of 0, 1, 2, or 3 amino acids.