24 results about "Activation lymphocyte" patented technology

The disclosure provides a method of treating a human subject afflicted with lung cancer (e.g., non-small cell lung cancer (NSCLC)) with a programmed death-1 (PD-1) pathway inhibitor (e.g., an anti-PD-1 antibody) and a concurrent chemoradiotherapy (CCRT, e.g., a platinum doublet chemotherapy (PDCT) and a radiation therapy) followed by a combination of a PD-1 pathway inhibitor (e.g., an anti-PD-1 antibody) and a lymphocyte activation gene-3 (LAG-3) antagonist (e.g., an anti-LAG-3 antibody). In some aspects, the method comprises a recovery period that begins upon completion of the treatment with the PD-1 pathway inhibitor and the CCRT and ends at the start of the treatment with the combination of the PD-1 pathway inhibitor and the LAG-3 antagonist.

The invention provides an application of a T lymphatic activation related cytokine as a biomarker in prediction of children immune globulin non-reactive Kawasaki disease. The team finds that in patients of an IVIG sensitive group and an IVIG non-response group, differences of expression levels of IL-6 and IL-17 before and after treatment have statistical significance; meanwhile, ROC curve analysis shows that IL-6 and IL-17 serve as early warning signals, and the prediction efficiency of the IVIG-unreacted Kawasaki disease is remarkably superior to that of existing prediction factors. Particularly, the levels of IL-6 and IL-17 are re-evaluated after initial treatment, so that the early prediction accuracy of the IVIG unresponsive Kawasaki disease can be further improved. By introducing IL-6 and IL-17 as novel biomarkers, early accurate prediction of the IVIG unresponsive Kawasaki disease is realized. Compared with the prior art, the method can provide a quicker and more accurate risk assessment basis for clinicians, so that early recognition of high-risk patients, optimization of subsequent treatment schemes and reduction of serious complications are facilitated, and a new thought and direction are provided for clinical diagnosis and treatment.

The present disclosure provides methods of treating a human subject suffering from lung cancer (e.g., non-small cell lung cancer (NSCLC)) using a programmed death-1 (PD-1) pathway inhibitor (e.g., an anti-PD-1 antibody) and synchronous chemoradiotherapy (CCRT, e.g., platinum-based dual drug chemotherapy (PDCT) and radiotherapy), a combination of a PD-1 pathway inhibitor (e.g., an anti-PD-1 antibody) and a lymphocyte activation gene-3 (LAG-3) antagonist (e.g., an anti-LAG-3 antibody) is then used. In some aspects, the methods include a recovery phase that begins after completion of treatment with a PD-1 pathway inhibitor and CCRT, and ends at the beginning of treatment with a combination of a PD-1 pathway inhibitor and a LAG-3 antagonist.

The present invention relates to the technical field of molecular immunology, and specifically discloses novel antigen polypeptides for lung cancer and their applications. The polypeptide comprises one or more amino acid sequences selected from those shown in, for example, PDGPPEKP (SEQ ID NO.1), MNKALLPAK (SEQ ID NO.2), and MYCELPDSF (SEQ ID NO.3); or is a polypeptide with the same or similar function obtained by substituting and / or deleting and / or adding at least one amino acid in the amino acid sequences of the above polypeptides. The novel antigen polypeptide for lung cancer provided by the present invention can bind to MHC class I molecules on human cells, can significantly stimulate the activation and expansion of T lymphocytes with tumor cell killing effects, and increase the killing ability of T cells against lung cancer cells. Therefore, the polypeptide can be used to prepare drugs for treating lung cancer, especially for preparing lung cancer cell vaccines. The antigen polypeptide can be used to treat lung cancer and prevent recurrence and metastasis in patients after surgery.

The disclosure provides fusion proteins specific for both CD137 and GPC3, which fusion protein can be used to co-stimulate lymphocyte activation in a GPC3-target-dependent manner. Such fusion proteins can be used in many pharmaceutical applications, for example, as anti-cancer agents and / or immune modulators for the treatment or prevention of human diseases such as a variety of tumors. The present disclosure also concerns methods of making the fusion proteins described herein as well as compositions comprising such fusion proteins. The present disclosure further relates to nucleic acid molecules encoding such fusion proteins and to methods for generation of such fusion proteins and nucleic acid molecules. In addition, the application discloses therapeutic and / or diagnostic uses of such fusion proteins as well as compositions comprising one or more of such fusion proteins.

Disclosed herein is a composition for enhancing an abscopal effect of radiation, including a lymphocyte activation gene-3 (LAG-3) inhibitor and a programmed cell death protein-1 (PD-1) inhibitor. One aspect relates to a method of enhancing an abscopal effect of radiation by co-administering a composition including an LAG-3 inhibitor and a PD-1 inhibitor in conjunction with radiotherapy in the treatment of cancer (e.g., triple-negative breast cancer).

The disclosure provides fusion proteins specific for both CD137 and GPC3, which fusion protein can be used to co-stimulate lymphocyte activation in a GPC3-target-dependent manner. Such fusion proteins can be used in many pharmaceutical applications, for example, as anti-cancer agents and / or immune modulators for the treatment or prevention of human diseases such as a variety of tumors. The present disclosure also concerns methods of making the fusion proteins described herein as well as compositions comprising such fusion proteins. The present disclosure further relates to nucleic acid molecules encoding such fusion proteins and to methods for generation of such fusion proteins and nucleic acid molecules. In addition, the application discloses therapeutic and / or diagnostic uses of such fusion proteins as well as compositions comprising one or more of such fusion proteins.

The present disclosure provides methods of treating a human subject afflicted with lung cancer (e.g., non-small cell lung cancer (NSCLC)) with a PD-1 (programmed death-1) pathway inhibitor (e.g., an anti-PD-1 antibody) and concurrent chemoradiotherapy (CCRT, e.g., platinum-doublet chemotherapy (PDCT) and radiation therapy), followed by a combination of a PD-1 pathway inhibitor (e.g., an anti-PD-1 antibody) and a lymphocyte-activation gene 3 (LAG-3) antagonist (e.g., an anti-LAG-3 antibody). In some embodiments, the methods include a recovery period that begins upon completion of treatment with the PD-1 pathway inhibitor and CCRT and ends upon initiation of treatment with the combination of the PD-1 pathway inhibitor and the LAG-3 antagonist.

Binding molecules that bind specifically to Lymphocyte-activation gene-3 (LAG-3) are described. The binding molecules inhibit T cell receptor (TCR)-mediated signal transduction in LAG-3 positive T cells through agonism of LAG-3. In some embodiments, the binding molecules bind specifically to a discontinuous epitope within the extracellular Ig superfamily domain D1 of a LAG-3 protein, wherein amino acid residues of the discontinuous epitope lie outside a 30 amino acid extra-loop sequence of the domain D1 of the LAG-3 protein. Use of the binding molecules as medicaments, in particular for the treatment of conditions associated with proliferation and / or activation of CD4+ and / or CD8+ T cells, in particular inflammatory and autoimmune disorders, is also described.

The present application provides a method of treating a cancer in an individual that involves administering to the individual a lymphocyte activating agent (e.g., a T cell activating agent) and an agent that inhibits SHP-1 signaling (e.g., TPI-1, PTP-1). In some cases, the method optionally further involves administering a TNFα inhibitor and / or a pro-inflammatory agent (such as TLR or STING agonists).

The present disclosure relates to systems and methods for immune therapy. For example, a method can be used to enhance the proliferation of chimeric antigen receptor (CAR) T cells in a subject, The method comprises administering to the subject an effective amount of a pharmaceutical composition comprising one or more lymphocyte activation agents and one or more recombinant viral particles comprising a polynucleotide encoding a CAR, wherein the proliferation of CAR T cells in the subject is greater than in a subject administered with the one or more recombinant viral particles but without the lymphocyte activation agent.

The present invention relates to the field of biotechnology, specifically to the immune effects and uses of farnesyl diphosphate, an intermediate metabolite of cholesterol synthesis. The present invention relates to the use of farnesyl diphosphate or its analogs, derivatives, potentiators, or inhibitors in regulating dendritic cell chemotaxis and / or lymphocyte activation, or in the preparation of a drug or kit for regulating dendritic cell chemotaxis and / or lymphocyte activation, as well as corresponding drugs or kits and methods of regulation. The present invention can be applied to regulating dendritic cell chemotaxis and / or lymphocyte activation, and / or further used to regulate the body's immune response and homeostasis, prevent and treat allergic diseases such as allergic rhinitis, autoimmune diseases such as systemic lupus erythematosus, and select tumor immunotherapy regimens and / or prognosis assessment, and has broad application prospects.

The present disclosure provides for compounds and methods of treating cancer, methods of increasing lymphocyte activation, and methods of activating TEC kinase.

The invention discloses an HLA-C restrictive SARS-CoV-2 lymphocyte antigen epitope peptide and application thereof, belongs to the fields of medical immunology and infectious pathology, and particularly relates to three thymus dependent lymphocyte antigen epitope peptides of SARS-CoV-2, the amino acid sequence of the epitope peptide is shown as any one of SEQ ID NO: 1-3, and the amino acid sequence of the epitope peptide is shown as any one of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6. Or an amino acid sequence obtained by substituting, deleting, inserting and / or adding one or more amino acid sequences in any sequence of SEQ ID NO: 1-3. The antigen epitope peptide can be presented by HLA-C0101 and HLA-C0602 molecules, and the activation, proliferation and differentiation of SARS-CoV-2 specific thymus dependent lymphocytes are stimulated, so that the immune effect of resisting SARS-CoV-2 infection is exerted; the antigen peptides can be used for preparing mixed polypeptide vaccines of SARS-CoV-2, recombinant protein vaccines connected with a plurality of epitope peptides in series and DNA and RNA vaccines, can be used for preparing a detection kit for detecting SARS-CoV-2 specific thymus dependent lymphocytes, and can also be used for preparing effector thymus dependent lymphocytes or drugs for treating SARS-CoV-2 infection. The SARS-CoV-2 antibody has a potential application value in the prevention, treatment and diagnosis of SARS-CoV-2 infection and COVID-19.

The invention discloses an SARS-CoV-2 lymphocyte antigen epitope peptide and application thereof, belongs to the fields of medical immunology and infectious pathology, and particularly relates to three thymus dependent lymphocyte antigen epitope peptides of SARS-CoV-2. The epitope peptide is characterized in that the amino acid sequence of the epitope peptide is shown as any one of SEQ ID NO: 1-3; or an amino acid sequence obtained by substituting, deleting, inserting and / or adding one or more amino acid sequences in SEQ ID NO: 1-3. The antigen epitope peptide can be presented by HLA-DR molecules, and stimulates activation, proliferation and differentiation of SARS-CoV-2 specific thymus dependent lymphocytes, so that the immune effect of resisting SARS-CoV-2 infection is exerted; the antigen peptides can be used for preparing mixed polypeptide vaccines of SARS-CoV-2, recombinant protein vaccines connected with a plurality of epitope peptides in series and DNA and RNA vaccines, can be used for preparing a detection kit for detecting SARS-CoV-2 specific thymus dependent lymphocytes, and can also be used for preparing effector thymus dependent lymphocytes or drugs for treating SARS-CoV-2 infection. The SARS-CoV-2 antibody has a potential application value in the prevention, treatment and diagnosis of SARS-CoV-2 infection and COVID-19.

To provide a combination therapy using a PD1-LAG3 bispecific antibody and a CD20 T cell activating bispecific antibody, use of the combination therapy for cancer treatment, and methods for using combination therapies.SOLUTION: Provided is an anti-CD20 / anti-CD3 bispecific antibody for use in the treatment of CD20-expressing cancer, where the anti-CD20 / anti-CD3 bispecific antibody is used in combination with an anti-PD1 / anti-LAG3 bispecific antibody, where the anti-PD1 / anti-LAG3 bispecific antibody comprises a first antigen binding domain that specifically binds to a programmed cell death protein 1 (PD1) and a second antigen binding domain that specifically binds to lymphocyte activating gene 3 (LAG3), where the first antigen binding domain that specifically binds to PD1 comprises a VH domain comprising a specific amino acid sequence and a VL domain comprising a specific amino acid sequence.SELECTED DRAWING: Figure 4

A assay for screening or determining the activity of a lymphocyte-activation gene 3 (LAG-3) agonist is described. According to the assay, a plurality of effector T cells is provided, each effector T cell expressing LAG-3 and a T cell receptor (TCR) on its surface and comprising a reporter gene encoding a reporter protein, wherein expression of the reporter protein is regulated by LAG-3-mediated inhibition of TCR signaling within the effector T cell. The activity of the agonist is determined according to the extent to which expression of the reporter protein is altered in the presence of the agonist as compared to expression of the reporter protein in the absence of the agonist. The assay can be used to determine the potency of a preparation of the agonist, as a quality control step in the production of the agonist, or for stability testing of a preparation of the agonist. A kit for performing the assay is also described.

The disclosure provides a method of treating a human subject afflicted with lung cancer with a lymphocyte activation gene-3 (LAG-3) antagonist. In some aspects, the method comprises combination of the LAG-3 antagonist with an additional therapeutic agent (e.g., a programmed death-1 pathway inhibitor) and / or anti-cancer therapy (e.g., chemotherapy such as a platinum doublet chemotherapy).

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 invention discloses an HLA-B restrictive SARS-CoV-2 lymphocyte antigen epitope peptide and application thereof, belongs to the fields of medical immunology and infectious pathology, and particularly relates to three thymus dependent lymphocyte antigen epitope peptides of SARS-CoV-2, the amino acid sequence of the epitope peptide is shown as any one of SEQ ID NO: 1-3, and the amino acid sequence of the epitope peptide is shown as any one of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6. Or an amino acid sequence obtained by substituting, deleting, inserting and / or adding one or more amino acid sequences in any sequence of SEQ ID NO: 1-3. The antigen epitope peptide can be presented by an HLA-B4601 molecule and an HLA-B4001 molecule, and is used for stimulating the activation, proliferation and differentiation of SARS-CoV-2 specific thymus dependent lymphocytes, so that the immune effect of resisting SARS-CoV-2 infection is exerted; the antigen peptides can be used for preparing mixed polypeptide vaccines of SARS-CoV-2, recombinant protein vaccines connected with a plurality of epitope peptides in series and DNA and RNA vaccines, can be used for preparing a detection kit for detecting SARS-CoV-2 specific thymus dependent lymphocytes, and can also be used for preparing effector thymus dependent lymphocytes or drugs for treating SARS-CoV-2 infection. The SARS-CoV-2 antibody has a potential application value in the prevention, treatment and diagnosis of SARS-CoV-2 infection and COVID-19.

The present application provides a method of treating cancer in a subject involving administering to the subject a bone marrow cell activator or therapy (e.g., a TLR agonist or STING agonist) and a TNF [alpha] inhibitor. In some cases, the methods further involve administering to the subject an SHP-1 inhibitor and / or a tyrosine kinase inhibitor, optionally further administering a lymphocyte activator (e.g., a cytokine (e.g., IL-2)) and / or an immune checkpoint inhibitor (e.g., anti-PD-1).

A method for preparing an activated expanded lymphocyte stock solution includes co-culturing, in a serum-free medium, a lymphocyte activator with peripheral blood mononuclear cells obtained via autologous peripheral whole blood centrifugal extraction, and thus completing lymphocyte culture activation. The cultured activated lymphocytes are placed into a serum-free medium. Subculturing is performed to prepare lymphocyte activation culture. A serum-free medium having a volume which is 5 to 10 times of the lymphocyte activation culture is added to the lymphocyte activation culture. Expansion culture is performed, wherein the number of expansion culture generations is 1 to 5. A step of centrifuging, washing, and collecting the activated expanded lymphocytes is performed. The activated expanded lymphocytes have high cell expansion efficiency, high cell viability, stable cell activity, a long effective period, safety, efficiency, and minimal side effects, and effectively solve a key problem of individualized immune cell tumor treatment technology.

Assays for screening or determining the activity of a lymphocyte activation gene 3 (LAG-3) agonist are described. According to the assays, a plurality of effector T cells are provided, each effector T cell expressing LAG-3 and a T cell receptor (TCR) on its surface, and comprising a reporter gene encoding a reporter gene, wherein reporter expression is regulated by LAG-3-mediated inhibition of TCR signaling within the effector T cells. Agonist activity is determined from the degree to which reporter expression is altered in the presence of the agonist compared to reporter expression in the absence of the agonist. The assays can be used to determine the potency of an agonist preparation as part of a quality control step in agonist production, or for stability testing of an agonist preparation. Kits for performing the assays are also described.

The disclosure provides a method of treating unresectable or metastatic melanoma in a human patient with a lymphocyte activation gene-3 (LAG-3) antagonist. In some aspects, the method includes a combination of the LAG-3 antagonist with a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor. In some aspects, the method includes one or more additional therapeutic agents and / or anti-cancer therapies.