77 results about "LAG3" patented technology

To provide antibodies that bind to lymphocyte activation gene 3 (LAG3) protein, which is a T cell co-inhibitor, and methods of use.SOLUTION: In various embodiments of the invention, the antibodies are fully human antibodies that specifically bind to LAG3. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing LAG3 activity, thus providing means of treating a disease or disorder such as cancer or viral infection. The antibodies of the present invention are useful, inter alia, for targeting immune cells expressing LAG3 and for modulating LAG3 activity.SELECTED DRAWING: None

The invention relates to bispecific antibodies comprising a first antigen binding domain that specifically binds to PD1 and a second antigen binding domain that specifically binds to LAG3. The invention further relates to methods of producing these molecules and to methods of using the same.

The disclosure provides a method for treating a subject afflicted with a tumor comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody or antigen-binding portion thereof or an anti-PD-L1 antibody or anti-gen-binding portion thereof, wherein the subject is identified as having a high inflammatory gene signature score. In some embodiments, the high inflammatory gene signature score is determined by measuring the expression of a panel of inflammatory genes in a tumor sample obtained from the subject, wherein the inflammatory gene panel comprises CD274 (PD-LI), CD8A, LAG3, and STAT1.

The invention relates to combination therapies employing an anti-PD1 / anti-LAG3 bispecific antibody and an HLA-G T cell-activating bispecific antibody, the use of these combination therapies for the treatment of cancer and methods of using the combination therapies.

Disclosed herein are multi-valent, multi-specific, single-chain antibodies with specificities for four antigens selected from EGFR, PD-L1, HSA, CD28, CD3E, OX-40, CD40, 4-1BB, LAG3, and CD16A.

The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1), a Lymphocyte-Activation Gene 3 (LAG3) antagonist, and all-trans retinoic acid or a pharmaceutically acceptable salt thereof and the use of the combination therapies for the treatment of cancer.

An engineered cell, expressing: (i) a PD1-binding molecule, wherein the PD1-binding molecule comprises a PD1-binding domain and a transmembrane domain, but does not comprise an intracellular domain other than that of a PD1 ligand; and (ii) an immunosuppressive molecule, which comprises an immunosuppressive protein-binding domain and a transmembrane domain, but does not comprise a primary signaling domain, wherein the immunosuppressive protein is selected from NKG2A, TIM3, LAG3, TIGIT, CTLA4, IRP60, SIRPα, KIR2DL1 / 2 / 3, and LILRB1, or combinations thereof. The present invention further relates to a composition comprising the engineered cell and a use of the engineered cell.

Described herein are LAG3 specific single domain antibodies and binding molecules comprising such single domain antibodies, as well as nucleic acids encoding the same. Also provided are nucleic acids (e.g., mRNA) encoding such single domain antibodies and binding molecules and delivery vehicles (e.g., lipid nanoparticles) formulated with said nucleic acids. The disclosure also features methods of using such antibodies, binding molecules, nucleic acids, and delivery vehicles formulated with said nucleic acids to treat various diseases such as inflammatory diseases, T cell driven autoimmune diseases, and cancer (e.g., solid tumors or hematological malignancies).

Antibodies that selectively bind to glycosylated LAG3 are provided compared to non-glycosylated LAG3. In some embodiments, LAG3 polypeptides that include glycosylated amino acid positions are also provided. Methods for producing and using such antibodies and polypeptides (e.g., for cancer treatment) are also provided.

Disclosed herein are monospecific and multispecific single chain antibodies having specificity for one or more of CD47, PD-L1, HSA, CD33, LAG3, and CD16.

Provided herein are methods of treating a cancer in a subject that include (a) administering to the subject a therapeutically effective amount of a composition comprising a MICAL2 inhibitor, and (b) administering to the subject a therapeutically effective amount of one or more checkpoint inhibitors selected from the group consisting of an IL1-alpha inhibitor, a PD-1 inhibitor, a LAG3 inhibitor, and a TIGIT inhibitor, thereby treating the cancer in the subject.

This invention relates to the application of LAG3 agonists in the preparation of drugs for hematoma clearance after intracerebral hemorrhage (ICH) and the application of LAG3 in regulating hematoma clearance after ICH, belonging to the field of biomedical technology. This invention utilizes a mouse ICH model to first inject a LAG3 neutralizing antibody (C9B7W) via orthotopic injection, clarifying that LAG3 can regulate the phagocytic function of microglia after ICH and participate in hematoma clearance, revealing its potential molecular target for enhancing microglia phagocytic function and promoting hematoma clearance. Furthermore, overexpression of LAG3 after ICH is demonstrated. Lag3 The study confirmed that enhanced phagocytic function of microglia accelerated hematoma clearance, demonstrating that LAG3 agonists can be used as drugs for hematoma clearance after intracerebral hemorrhage. The experimental results of this invention make it possible to apply LAG3 to the prognostic treatment of ICH, thereby advancing basic and clinical research on endogenous hematoma clearance after ICH.

Disclosed herein are monospecific and multispecific single-chain antibodies specific for one or more of CD47, PD-L1, HSA, CD33, LAG3, and CD16.

Disclosed herein are monospecific and multispecific antibodies specific for CD28 and CD3E, and one or more of OX-40, CD40, 4-1BB, HSA, IL-22, PD-L1, CD16, CD47, CD33, LAG3, and EGFR.

The present invention relates to a combination therapy using an anti-PD1 / anti-LAG3 bispecific antibody and an HLA-G T cell activating bispecific antibody, the use of this combination therapy for the treatment of cancer, and a method for using this combination therapy.

This disclosure provides a method for treating a cancer patient comprising administering to the patient a therapeutically effective amount of an anti-PD-1 antagonist, for example, an anti-PD-1 or anti-PD-L1 antibody, in combination with an indolamine 2,3-dioxygenase inhibitor, wherein the patient is identified as exhibiting a combined biomarker comprising (a) a high IFNγ inflammatory signature score and (b) a low tryptophan 2,3-dioxygenase 2 (TDO2) gene expression score. The high IFNγ inflammatory signature score is determined by measuring the expression of a panel of IFNγ-related inflammatory genes in a cancer sample obtained from the patient, wherein the gene panel comprises, for example, IFNγ, CXCL10, CXCL9, HLA-DRA, IDO1, and STAT1. In some respects, the gene panel also includes CCR5, CXCL11, GZMA, and PRF1.In some aspects, the genetic panel comprises CXCR6, TIGIT, PD-L1, PD-L2, LAG3, NKG7, PSMB10, CMKLR1, CD8A, IDO1, CCL5, CXCL9, HLA.DQA1, CD276, HLA.DRB1, STAT1, HLA.E and TDO2.

Disclosed herein are engineered polyfunctional CD4+ T cells / CAR T cells and methods of their use for the treatment of cancers. One embodiment provides a method of producing polyfunctional CD4+ T cells by constitutively activating STAT5A in the cells to induce a polyfunctional phenotype. Also provided is a method of reversing exhaustion in tumor-specific CD4+ T cells by engineering the cells to express Fos, Jun, Nr4a1, or combinations thereof but not express Tox, Pdcd1, Ctla4, Haver2, Lag3, Tigit, Slam6, Nrf4a2, and administering the engineered cells to a subject.

The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and / or treating an infectious disease with such molecules are provided.

The disclosure provides a method for treating a subject afflicted with a cancer comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antagonist, e.g., an anti-PD-1 or anti-PD-L1 antibody, in combination with an indoleamine 2,3-dioxygenase inhibitor, wherein the subject is identified as exhibiting a combined biomarker comprising (a) a high IFNγ inflammatory signature score and (b) a low tryptophan 2,3-dioxygenase 2 (TDO2) gene expression score. The high IFNγ inflammatory signature score is determined by measuring the expression of a panel of IFNγ related inflammatory genes in a cancer sample obtained from the subject, wherein the gene panel comprises, e.g., IFNγ, CXCL10, CXCL9, HLA-DRA, IDO1, and STAT1. In some aspects, the gene panel further comprises CCR5, CXCL11, GZMA, and PRF1. In some aspects, the gene panel comprises CXCR6, TIGIT, PD-L1, PD-L2, LAG3, NKG7, PSMB10, CMKLR1, CD8A, IDO1, CCL5, CXCL9, HLA.DQA1, CD276, HLA.DRB1, STAT1, HLA.E, and TDO2.

The application provides a CAR-T cell overexpressing an IFITM2 gene, a construction method and application thereof in immune cell therapy, and relates to the technical field of biological medicine.The application takes CD276 as a target, regulates T cell memory differentiation and anti-exhaustion mechanism through overexpression of the IFITM2 gene, so that the treatment effect and persistence of CAR-T cell therapy are improved.The CD276-IFITM2 CAR-T cell constructed in the application has more memory differentiation phenotypes and fewer exhaustion phenotypes compared with the CD276 CAR-T cell, and through inhibition of PD-1 and LAG3, strong anti-exhaustion characteristics are realized.Meanwhile, the CD276-IFITM2 CAR-T cell significantly improves the expression level of IL-2, TNF alpha and IFN gamma under multiple antigen stimulations, and has the ability to continuously produce anti-cancer functional factors.In addition, the CD276-IFITM2 CAR-T cell has more significant tumor inhibition effect compared with the CD276 CAR-T cell.The CD276-IFITM2 CAR-T cell provided in the application can be used for preparing a drug for immune cell therapy.

This disclosure provides nucleic acids encoding peptides which bind to LAG3 and can be used to block the interaction of LAG 3 with other molecules such as MHC-II, FGL1, and α-synuclein. These peptides can be used for various therapeutic purposes, such as inhibiting the progression of a hyperproliferative disorder, including cancer, or inhibiting the progression of a synucleinopathy, inhibiting the progression of sepsis, inhibiting the progression of an infectious disease, and enhancing a response to a vaccine.

The application belongs to the field of immunology and relates to an anti-LAG3 single-domain antibody and use thereof.The single-domain antibody is composed of a heavy chain, the heavy chain comprising heavy chain CDR1 shown in any one of SEQ ID NO:22-SEQ ID NO:26, heavy chain CDR2 shown in any one of SEQ ID NO:27-SEQ ID NO:29, and heavy chain CDR3 shown in any one of SEQ ID NO:30-SEQ ID NO:34.The beneficial effect of the application relative to the prior art is that the application uses biological genetic engineering technology to screen out a single-domain antibody specific to LAG3, and the antibody has good affinity.

The invention relates to a molecular marker for immunotherapy prediction of a targeting shower cell and application of the molecular marker, and belongs to the technical field of molecular biology. The invention provides a molecular marker for immunotherapy prediction of a targeting shower cell. The molecular marker comprises CD8, CD4, PD-1, Foxp3, CD19 and CD3, wherein the CD8, the CD4, the PD-1, the Foxp3, the CD19 and the CD3 are used for immunotherapy prediction; or comprises a CD45, a CD45RA, a CD45RO, a CD25, a CCR7 and a CD127; or comprises CD3, LAG3, Tim3, ICOS, CD69 and CD103; or comprises a CD79A, a CD79B, a CD20, a CD21 and a CD138; or the CD56, the CD161, the CD57, the CD94 and the Granzyme B are included; the invention relates to a CD56, CD161, CD57, CD94 and Granzyme B. The CD56, the CD161, the CD57, the CD94 and the Granzyme B. The molecular marker can accurately distinguish shower cell groups and interaction.

The present application provides antibodies that selectively bind to glycosylated LAG3 relative to unglycosylated LAG3. In some aspects, the present application also provides LAG3 polypeptides comprising glycosylated amino acid positions. The present application also provides methods of making and using such antibodies and polypeptides (e.g., for treating cancer).

The present disclosure provides stable pharmaceutical formulations comprising anti- LAG3 antibodies and anti-PD-1 antibodies. In certain embodiments, the formulations further comprise a buffer, an amino acid, a non-ionic surfactant and a sugar. The pharmaceutical formulations exhibit a substantial degree of antibody stability upon stress and storage. In certain aspects, the stable pharmaceutical formulations are used in methods of treating a cancer, the methods comprising administering the disclosed pharmaceutical formulation to a subject in need thereof.

Provided is a novel protein or the like in the form of a trispecific triantibody having an increased anti-tumor effect. The present invention relates to a fusion protein comprising two different chains, i.e., a first chain and a second chain, in which three kinds of combinations of VH / VL binding domains formed in the fusion protein have any kind of binding ability selected from the group consisting of (i) binding ability to 5T4, (ii) binding ability to a CD3 receptor complex of a T cell, and (iii) binding ability to PD-1, PD-L1, or LAG3. The three combined VH / VL binding structural domains have different binding capacities. ).

Disclosed herein are multivalent, multispecific single-chain antibodies having specificity for four antigens selected from the group consisting of EGFR, PD-L1, HSA, CD28, CD3E, OX-40, CD40, 4-1BB, LAG3, and CD16A.

The invention relates to the technical field of bioengineering, in particular to an LAG3 shear variant and application thereof. The nucleotide sequence of the splicing variant of the LAG3 provided by the embodiment of the invention is as shown in SEQ ID No. 1. Compared with an existing shear variant, the LAG3 new shear variant provided by the invention can better promote proliferation of a hepatoma cell line, and inhibition of expression of the LAG3 new shear variant can remarkably reduce growth of the hepatoma cell line, so that the specificity of a coding region of the LAG3 new shear variant has a wide application prospect in the aspects of diagnosis and treatment of hepatoma.

This invention provides a method for screening peptides that specifically target T cells, comprising providing T cells having a subset selected from CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD16, CD25, CD26, CD27, CD28, CD30, CD38, CD39, CD40L, CD44, CD45, CD62L, CD69, CD73, CD80, CD83, CD86, CD95, CD103, CD119, CD126, CD150, CD152 (CTLA-4), CD153, CD154 (CD40L) The T cells are labeled with at least one of the following surface antigen markers: CD161, CD183, CD223, CD254, CD275, CD45RA, CXCR3, CXCR5, FasL, IL18R1, CTLA-4, OX40, GITR, LAG3, ICOS, PD-1, leu-12, TCR, TLR1, TLR2, TLR3, TLR4, TLR6, NKG2D, CCR, CCR1, CCR2, CCR4, CCR6, and CCR7. The T cells are then contacted with a peptide display library, and target peptides that specifically bind to the T cells are screened therefrom.

Provided herein are methods of treating a cancer in a subject that include (a) administering to the subject a therapeutically effective amount of a composition comprising a MICAL2 inhibitor, and (b) administering to the subject a therapeutically effective amount of one or more checkpoint inhibitors selected from the group consisting of an IL1-alpha inhibitor, a PD-1 inhibitor, a LAG3 inhibitor, and a TIGIT inhibitor, thereby treating the cancer in the subject.