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

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 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).

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.