61 results about "LAG3" patented technology

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.

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.

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.

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.

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.

The embodiments of the present application provide a method for establishing in vitro CD8 + T cell exhaustion model and application thereof. The method comprises: using T cell receptor signal stimulator combined with interleukin-10 to continuously stimulate CD8 + T cells under in vitro culture conditions. The cells induced by the method not only highly express exhaustion key transcription factor TOX and various surface inhibitory receptors (such as PD1, TIM3, LAG3 and the like), but also significantly reduce the secretion ability of effector cytokines, highly reduce the real exhaustion performance in in vivo chronic infection or tumor microenvironment in vitro, and effectively overcome the defect of few CD8 + T cells in traditional in vivo animal model, and high-quality exhaustion cells can be obtained in vitro in large scale in only 6 to 8 days.

The present disclosure provides methods for treating multiple myeloma. In certain embodiments, the present methods comprise administering to a subject in need thereof a BCMA inhibitor (e.g., a bispecific antibody or antigen-binding fragment thereof that binds to BCMA and CD3) in combination with a LAG3 inhibitor (e.g., an anti-LAG3 antibody). In certain embodiments, the subject has been previously treated with one or more anti-cancer therapies.

The invention provides a CAR-T cell overexpressing an IFITM2 gene, a construction method and application of the CAR-T cell in immune cell therapy, and relates to the technical field of biological medicine. According to the invention, CD276 is taken as a target spot, and the T cell memory differentiation and anti-depletion mechanism is regulated and controlled by overexpressing the IFITM2 gene, so that the treatment effect and durability of the CAR-T cell therapy are improved. Compared with the CD276CAR-T cell, the CD276-IFITM2CAR-T cell constructed by the invention has more memory differentiation phenotypes and less depletion phenotypes, and a relatively strong depletion resistance characteristic is realized by inhibiting PD-1 and LAG3. Meanwhile, the CD276-IFITM2CAR-T cell can obviously improve the expression levels of IL-2, TNF alpha and IFN gamma under the stimulation of multiple antigens, and has the capability of continuously generating anti-cancer functional factors. In addition, compared with the CD276CAR-T cell, the CD276-IFITM2CAR-T cell disclosed by the invention has a more remarkable tumor inhibition effect. The CD276-IFITM2CAR-T cell provided by the invention can be used for preparing a medicine for an immune cell therapy.

The present invention relates to the field of biomedicine. Provided are a monoclonal antibody targeting human HHLA2, and a multifunctional fusion antibody molecule derived therefrom. The HLLA2 monoclonal antibody can bind to an HLLA2 antigen with high specificity, and effectively block an immunosuppressive signaling pathway between the antigen and a receptor KIR3DL3, thereby relieving the functional inhibition of T cells and enhancing the tumor-killing function of NK cells. On the basis of the antibody scaffold, a fusion antibody comprising a plurality of immunomodulatory domains is constructed, wherein the domains comprise, but are not limited to, an anti-PD-L1 antibody or anti-PD-1 antibody or anti-CD3 antibody domain, a CD86 / CD80 variant polypeptide, and an LAG3 variant polypeptide. The fusion antibody can synergistically block a plurality of immune checkpoint pathways, activate costimulatory signals, promote maturation of antigen-presenting cells, and enhance activation and killing functions of T cells. The provided antibody molecule can be used for preparing immunotherapy drugs for a variety of indications, is especially suitable for the treatment of solid tumors or hematologic tumors, and thus has significant application potential in terms of enhancing anti-tumor immune responses.

Provided is a method for screening polypeptides that specifically target T cells, comprising: providing T cells having a surface antigen marker selected from at least one of 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), 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; and contacting the T cells with a polypeptide display library, and screening therefrom target polypeptides that specifically bind to the T cells.

To provide methods of separating host cell lipases from an anti-LAG3 antibody or antigen binding fragment in chromatographic processes.SOLUTION: Provided is a method of separating a host cell lipase from a composition comprising an anti-LAG3 antibody or antigen-binding fragment and a host cell lipase through a hydrophobic interaction chromatographic (HIC) process, the method comprising: (a) passing a load fluid comprising the composition through HIC resin under a loading operating condition; and (b) collecting the anti-LAG3 antibody or antigen-binding fragment in a flowthrough. A separation factor (α) is the ratio of the partition coefficient (Kp) for the lipase to Kp for the anti-LAG3 antibody or antigen-binding fragment, log α is larger than 0.5 under the loading operating condition, and the anti-LAG3 antibody or antigen binding fragment comprises (a) light chain CDRs of specific sequences, and (b) heavy chain CDRs of specific sequences.SELECTED DRAWING: Figure 3